MXPA00004773A - Methods and compositions for the treatment of psoriasis - Google Patents

Abstract

This invention provides methods of treating psoriasis which entail eliciting an immune response in an individual against an antigen aberrantly expressed in psoriatic tissue, such as a ganglioside, in an individual. The anti-ganglioside immune response is elicited by administration of an antigen such as a ganglioside, an anti-idiotype moiety for a ganglioside, or a polynucleotide encoding an anti-idiotype moiety. Also described is a strategy for developing additional compositions for psoriasis. The compositions elicit an immunological response against a target antigen present on psoriatic tissue, which in turn can be detected using antibody affinity-purified from the serum of the treated subject. The presence of the immunological response correlates positively with control or resolution of the psoriatic symptoms.

Description

METHODS AND COMPOSITIONS FOR THE TREATMENT OF PSORIASIS BACKGROUND OF THE INVENTION Psoriasis is a chronic condition that affects more or less 2.6% of the population of the developed world. A recent study reported by the National Psoriasis Foundation estimates that 6.4 million people suffer from psoriasis, of which approximately 500,000 are classified as severe cases. The annual cost per patient for the treatment of psoriasis is currently estimated at 1.6 to 3.2 billion dollars. Each year, approximately 400 people are classified as disabled by the Social Security Administration, and another 400 people die of causes related to psoriasis.

Characteristics of Psoriasis It is not known what causes psoriasis, although there is evidence of a predisposition REF .: 120329 genetics and an autoimmune etiology. The onset can be triggered by systemic infections such as strep throat, skin damage, vaccines, and certain oral medications such as steroids. Subsequently, it is thought that the immune system induces inflammation and excessive reproduction of skin cells, which can be exacerbated by additional factors such as stress and diet. In normal skin, the time for a cell to move from the basal layer through the granular layer is 4 to 5 weeks. In psoriatic lesions, time is decreased 7 to 10 times due to a shortened cell cycle time, an increase in the absolute number of cells capable of proliferating, and an increased rate of division. The immune responses mediated by T cells seem to be responsible for the inflammation and hyperproliferation of keratinocytes. Neutrophils are found in psoriatic lesions, associated with increased levels of plasminogen activator. Psoriatic fibroblasts have increased levels of enzymes involved in the synthesis of collagen, secondary to the expansion of the capillary dermis. The psoriatic plaques comprise HLA-DR positive keratinocytes and Langerhans cells, and activated T cells expressing high levels of IL-2 receptors. The typical lesion of psoriasis is a well-demarcated erythematous plaque covered by thick, silver scales. Psoriasis can become so extensive as to cause the erythroder to exfoliate, in which the entire epidermal surface is in a state of hyperproliferation. Gluttate psoriasis is a form of the disease after streptococcal pharyngitis, with lesions of 1 to 3 cm characteristic, widely distributed. Pustular psoriasis is characterized by numerous sterile pustules 2 to 5 cm in diameter, and can lead to an episode of acute, explosive, life-threatening fever, chills, leukocytosis, hypoalbuminemia, and hypocalcemia, which demand immediate vigorous therapy. Plaque-type psoriasis previously stable may be acutely exacerbated by viral infections, particularly HIV. Psoriasis is also associated with five different forms of psoriatic arthritis, including distal intra-pharyngeal involvement; an oligoarticular asymmetric pattern; a symmetric polyarthritis; arthritis mutilans; and sacroilitis and spondylitis. The inflammation and hyperproliferation of psoriatic tissue is associated with a different histological and antigenic profile than normal skin. Dabelsteen and colleagues used a panel of anti-carbohydrate monoclonal antibodies to compare psoriatic tissue with the neighboring dermis. The pattern of glycosylation in the psoriatic epithelium is changed in two ways: some carbohydrates are expressed at an earlier stage of cell maturation. In addition, certain biosynthetic precursor antigens not expressed in normal skin were found in psoriatic skin. Paller et al. (1989) investigated the distribution of ganglioside GM3 using an antibody designated 8G9D8. At the electron microscope level, the deposition of the antibody was observed in the envelope of the corneocytes. The disposition was significantly diminished or absent in disorders of excessive keratinocyte proliferation, including squamous cell carcinomas, congenital ichthyosiform erythroderma, prokratosis, and psoriasis. In a subsequent study, Paller et al. (1993) found that when GM3 was added to normal foreskin keratinocytes, the skin with lesions of patients with psoriasis or ichthyosis, and cutaneous squamous cell carcinoma lines, this inhibited development in a dose-dependent, at concentrations of 10 to 100 μM. Confluent undifferentiated keratinocytes were less sensitive. Gangliosides GD3, 9-0-acetyl-GD2 and GDlb also inhibited the proliferation of keratinocytes. Gangliosides GM1 and GDla, and sialic acid had little effect. The authors concluded that the preferential activation of sialyltransferase II may be involved in the control of keratinocyte growth, but not with differentiation. Concharen et al studied the expression of gangliosides on the erythrocytes and sera of normal subjects, and patients with psoriasis. During the exacerbation phases, a marked decrease in the content of the GM2 and GM3 fractions of the red cells was observed, and GDla decreased in serum. The presence of a new fraction of monosialoganglioside was noted during the exacerbation, both in serum and in red cells. The ganglioside spectrum of patients, in the clinical remission of psoriasis, was almost normal. Heidenheim et al. Describe a monoclonal antibody designated UM4D4 which recognizes the cell surface marker, CDwβO. This marker "is present on a subgroup of normal T cells, melanocytes," malignant melanoma cells, and hyperproliferative psoriatic keratinocytes. The CDw60 antibodies bind to an acetylated form of GD3. 74% of basal cell carcinomas express CD60, while CD50 expression in normal skin is confined to melanocytes and a few scattered keratinocytes, in the basal cell layer. Skov and colleagues recently reported that in psoriatic skin, basal and suprabasal keratinocytes express CD60. The cloned T cell lines, obtained from skin with lesions after onset, were found to release a cocktail of soluble factors including IL- 4 and IL-13, which upregulated the expression of CDw60 on normal cultured keratinocytes.

Treatments currently available for psoriasis Classical treatments of psoriasis include calciptriene (a derivative of vitamin D3), topical preparations of coal tar, systemic antimitotic agents such as methotrexate, and retinoids, particularly etretinate. Extensive psoriasis can be treated by photosensitization with oral 8-methoxypsoralen, followed by ultraviolet light A. Corticosteroids are administered for psoriatic arthritis and acute attacks of pustular psoriasis. More recently, cyclosporin A has been tested in clinical trials at doses of 3-7 mg / kg with promising results, but associated with the risk of renal toxicity. There is no cure. Current biotechnology approaches or approaches for the treatment of psoriasis refer to a direct attack mediated by the drug, either on cell proliferation or on the immune component of the disease. Japanese patent application JP 6145069 describes angiogenesis inhibitors comprising ganglioside GM3 or a GM3 analogue as an active agent. At 100 μg / ml, GM3 showed normal human antiendothelial cell development of 4.5 x 104 on day 5, compared to 76 x 104 in controls. U.S. Patent No. 5,339,977 describes n-desacetyl-lysoganglioside derivatives for use as phospholipase A2 inhibitors, for the treatment of proliferative and autoimmune diseases, including various forms of cancer, psoriasis, and rheumatoid arthritis. A fusion toxin with IL-2 has been developed (Seragen, Inc.) that is designed to selectively destroy activated T cells in psoriatic plaques, leaving normal cells alone. The objective is to destroy the activated T cells, and with this to clear the psoriasis. A phase II study was conducted in which the test doses of 5, 10 and 15 μg / kg were administered per day. Comparable improvement was observed in patients with moderate to severe psoriasis. However, in order to obtain this response, the compound was administered three days per week, for four weeks. Various formulations containing the compound BCX-34 for psoriasis, cutaneous T-cell lymphoma, and HIV infection have been tested (Bioworld Today, Sep. 29, 1997; see also WO 95/01355; WO 93/21187;; WO 90/10631; U.S. Patent Nos. 5,008,270, 5,008,265, and 4,985,434), BCX-34 is a small molecule drug that inhibits the phosphorylase of the nucleoside purine, a human enzyme thought to be involved in the proliferation of T cells. An oral formulation is being tested in a Phase I / II trial in progress. An advanced topical formulation for the Phase III stage for lymphoma and psoriasis. The study of psoriasis in Phase III showed only a 14% improvement in average lesion scales in the treated group, compared to the placebo, which for these studies are not statistically significant. Accordingly, there is a need for therapeutic compositions that are effective in the management of psoriasis, particularly if they are effective when administered on an occasional basis. The present invention relates to a strategy in which the patient's own immune system is recruited in an active role against the disease.

BRIEF DESCRIPTION OF THE INVENTION The invention provides methods for using compositions that promote an immune response against an antigen, which is aberrantly expressed in psoriatic tissue. Accordingly, in one aspect, the invention provides methods for treating psoriasis in an individual, comprising administering an effective composition for stimulating a specific immune response against an antigen aberrantly expressed in human psoriatic tissue. This or these compositions comprise an antigen that shares immunological characteristics of an antigen that is aberrantly expressed in psoriatic tissue (such as human psoriatic tissue). Aberrantly expressed antigens in psoriasis include, but are not limited to gangliosides. While a detectable immune response is likely to be beneficial, efficacy may also be inferred by an improvement in symptoms or in the control of the psoriatic condition, beyond what might be expected without treatment.

Certain embodiments of the invention include methods for the treatment of psoriasis in an individual administration by eliciting an anti-ganglioside immune response in the subject. The immune response can be elicited using any suitable immunogen and / or suitable immunogenic composition, such as: (1) a ganglioside in an immunogenic form, such as GM2, GM3, GD1b, GD2, 9-0-acetyl-GD2, GD3, GD3-lactone, 9-O-acet Ü-GD3, and GT3; (2) an anti-idiotype for a ganglioside, - such as monoclonal antibodies 1A7, 4B5, or BEC-2; or (3) a polynucleotide that codes for an anti-idiotype for a ganglioside. The immune response can have humoral or cellular components, and preferably it has both. Additional embodiments of the invention relate to the preparation of a composition for use in the treatment of psoriasis by preparing a composition comprising the determinant in an immunogenic form, or even producing an anti-idiotype against a monoclonal antibody that it binds to the antigenic determinant. Also exemplified are methods for selecting a composition for efficacy in the treatment of psoriasis, which involves the administration of the composition to human subjects, and periodically checking the progression of the disease (optionally in combination with immunological parameters) after treatment. A further embodiment of the invention is a composition containing a ganglioside, an anti-idiotype for a ganglioside, or a polynucleotide encoding a ganglioside, packaged with an indication of its fitness for use in the treatment of psoriasis. Additional embodiments of the invention relate to the use of a component selected from the group consisting of a ganglioside, an anti-idiotype for a ganglioside, and an expression vector encoding an anti-idiotype for a ganglioside, in the manufacture of a medication for the treatment of psoriasis.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a scheme for evaluating the effect of elevating an anti-GD2 immune response using an anti-idiotype vaccine to treat modalities with severe chronic plaque psoriasis.

Figure 2 is a description of the cDNA sequence (SEQ ID NO: 1) and the amino acid sequence (SEQ ID NO: 2) of the light chain variable region of 1A7 and the attached residues. Figure 3 is a description of the cDNA sequence (SEQ ID No. 3) and the amino acid sequence (SEQ ID No. 4) of the heavy chain variable region of 1A7 and the attached residues.

DETAILED DESCRIPTION An objective of this invention is to provide the compositions that are newly applied in the treatment of psoriasis in its various manifestations. Ideally, the compositions promote the resolution of the clinical features, but the stabilization of the condition is a satisfactory result. It is desirable that the effect be lasting, so that once an effect is achieved, the readministration of the composition, if any, needs to occur only on an occasional basis. To achieve this, the usual way is to recruit the active participation of the host immune system, to react against a target antigen on the psoriatic tissue.

This invention is based in part on the discovery that. Systemically immunized patients with a suitable vaccine composition mount a response directed against a specific antigen of psoriasis. As illustrated in Example 3, the response includes circulating antibodies that adhere specifically to the affected tissue. Without pretending to be committed to any theory, it may be that the immune response to the target antigen promotes the elimination or metabolic down-regulation of the cells carrying the target antigen, or that it mechanically interferes with a pathological phenotype of the affected cells (such as the proliferation) that is mediated, at least in part, by the target antigen. As a result, the presence of the immune response promotes the chemical resolution of the condition. It is believed that several target antigens are suitable as vaccine targets in psoriasis, and various types of vaccines can be used to obtain the desired result. • Illustrative examples are given in the following sections.

Definitions With reference to the therapeutic methods and compositions of this invention, the term 'psoriasis' refers to all conditions of the skin in the clinical techniques described by this term, and to the conditions associated with psoriasis, including psoriatic arthritis. " "Psoriatic tissue" refers to the tissue affected by psoriasis and the affected cells contained within the tissue, but not to the cells that have migrated to the site, such as leukocytes. Preferably, the psoriatic tissue is from a human. The particular molecules referred to in this description, such as CEA, gangliosides designated GM1, GM2, and so on, are understood to include not only the intact molecule, but also the allotypic and synthetic variants, the synthetic analogs, the fusion molecules, the conjugates, and other derivatives that contain the progenitor molecule and its fragments, which are recognized by the specific antibodies for the intact molecule.

An "effective amount" is an amount sufficient to effect a beneficial or desired clinical result An effective amount may be administered in one or more doses For the purpose of this invention, an effective amount of ganglioside, antibody, or other composition in a amount that induces an immune response against an antigen of psoriasis Immunological activity "of a particular immunogen or vaccine component refers to the ability to raise an immune response. A specific immune response may comprise the antibody, B cells, T cells, and any combination thereof, and the effector functions resulting therefrom. Functions mediated by ADCC antibody and complement mediated cytolysis (CMC) are included. A T-cell response may include the function of helper T cells, the function of cytotoxic T cells, or the function of inflammatory / inducing T cells. A compound or composition capable of promoting a specific immune response according to any of these criteria is termed as * immunogenic. " An antigen that 'shares immunological characteristics' with another antigen, is an antigen that, when administered in an appropriate manner (such as, for example, alone, in conjunction with an adjuvant, associated with (or conjugated to) a compound), promotes An Immunological Activity For the purposes of this invention, it is also understood that an antigen comprises one or more antigenic determinants (as is well understood in the art.) A 'polynucleotide' is a polymeric form of nucleotides of any length, which contain deoxyribonucleotides, ribonucleotides, and nucleotide analogs in any combination. A "vector" refers to a recombinant DNA or RNA plasmid or virus, which comprises a heterologous polynucleotide that is to be distributed to a target cell, either in vi tro or in vi V. The terms' polypeptide ',' peptide "and" protein "are used interchangeably to refer to polymers of amino acids of any length, and may be interrupted by non-amino acids. An "aberrantly expressed antigen" is an antigen that is uniquely expressed, overexpressed and / or under-expressed in conjunction with a disease state.For purposes of this invention, the disease state is psoriasis.An "immunogenic form" of a antigen is a form of or formulation comprising the antigen that makes the antigen immunogenic. Such forms include, but are not limited to, the antigen alone, the antigen in conjunction with one or more adjuvants, the antigen in association with or conjugated to a portion, such as a hapten.A "host cell" denotes a eukaryotic cell. which has been genetically altered, or is capable of being genetically altered by administration of an exogenous polynucleotide, such as a plasmid or recombinant vector. When reference is made to genetically altered cells, the term refers to the originally altered cell, and its progeny. A polynucleotide, polypeptide, ganglioside, or other "isolated" component is one that is substantially free of the materials with which it is naturally associated Substantially free means at least 50%, preferably at least 75%, more preferably at least 90%, and even more preferably at least 98% free of the materials with which it is associated in nature, different from the solvent A "vaccine" is a pharmaceutical composition for human or animal use, which is administered with the intention to confer on the patient a degree of specific immunological reactivity against a particular objective, or a group of objectives. The immunological reactivity may be desired for experimental purposes, for the treatment of a particular condition, for the removal of a particular substance, or for prophylaxis. An active vaccine is a vaccine designed to promote an immune response in the patient, which persists in the absence of the components of the vaccine. "Adjuvant" as used herein in the context of a pharmaceutical composition, is a chemical or biological agent given in combination with an antibody, polynucleotide or polypeptide to increase its immunogenicity .An "individual" or "subject" treated according to This invention is a vertebrate, preferably a mammal, more preferably a human mammal Mammals include, but are not limited to, farm animals, sport animals, rodents, primates, and pets.

Other terms used in this description are explained where they arise.

General techniques The practice of the present invention will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are within the skill in the art. Such techniques are fully explained in the literature, such as' Molecular Cloning: A Laboratory Manual ', second edition (Sambrook et al., 1989), '01 igunucleotide Synthesis' (M.J. Gait, ed., 1984); 'Animal Cell Culture' (R. Freshney, ed., 1987); 'Methods in Enzymology' (Academic Press, Inc.); 'Handbook of Experimental Immunology' (D.M. Weir &C.C. Blackwell, eds.), 'Gene Transfer Vectors for Mammalian Cells' (J.M. Miller &M.P. Calos, eds., 1987); 'Current Protocols in Molecular Biology' (F.M. Ausubel et al., Eds., 1987); 'PCR: The Polymerase Chain Reaction', (Mullis et al., Eds., 1994); 'Current Protocols in Immunology' (J.E. Coligan et al., Eds., 1991).

All patents, patent applications, articles and publications mentioned herein, above and below, are incorporated by reference herein.

Target antigens in the psoriatic tissue The target antigen against which a specific immune response is desired contains an epitope or antigenic determinant which is aberrantly expressed in the psoriatic tissue. This means that it is present in the cells of the affected tissue (or the surrounding medium) in a way that makes it accessible to the immune system at a level that is significantly different than in the cells of the same type of tissue that are not affected. The cells in which the epitope is aberrantly expressed will be the cells resident in the affected area, particularly the keratinocytes or living epithelial cells, instead of the migrating cells. For purposes of this invention, the compositions described herein may comprise an antigen or an antigenic determinant. The aberrantly expressed antigenic determinant of interest may be of any chemical nature, including but not limited to protein epitopes, carbohydrate epitopes, and glycolipids such as gangliosides. Typically, the epitope is expressed uniquely and / or overexpressed in psoriatic tissue in a variety of different individuals, although variations in the level of expression may occur. Typically, the determinant will be expressed on the cell surface or will be present as an insoluble but accessible antigenic mass, instead of being a soluble factor. Histocompatibility antigens of Class I or Class II are excluded by definition. Antigenic determinants that are aberrantly expressed can be identified by a number of techniques known in the art. One method is to look for a particular messenger RNA transcript, which is present in an unusual abundance in the affected cells. Where the determinant is a protein antigen synthesized by the cell, a suitable substitute is, for example, the mRNA encoding the antigen. Where the determinant is a carbohydrate or glycolipid, a suitable substitute is, for example, mRNA that codes for an enzyme involved in the formation of a critical antigen-specific bond, in the synthetic route. The methods for the determination of the mRNA that is in an unusual abundance in one cell that in another involves the preparation of the mRNA from both cells, and then the amount of each particular mRNA is compared between the preparations. A number of techniques for the comparison step are related in some way to subtractive hybridization. One example involves the production of positive and negative cDNA, respectively, from the first and second RNA preparations, and looking for the cDNA that is not completely hybridized by the opposite preparation. Subtractive hybridization is described in standard molecular biology reference books, previously listed. Another way to compare the production of the particular messenger RNA is through differential visual representation. This has been extensively described by Liang et al. (1992, 1995), and has since been elaborated in a number of different ways. In this technique, the cDNA is prepared only from a subpopulation of each RNA preparation, and expanded via the polymerase chain reaction using primers of particular specificity. Similar subpopulations are compared through several RNA preparations for expression of differences by gel autoradiography. In order to monitor the RNA preparations completely, the assay can be repeated with a broad set of PCR primers. The selection strategy more effectively includes positive and negative, multiple control samples (Sunday et al.). By excising the corresponding region of the separation gel, it is possible to recover and sequence the cDNA. Antigenic determinants that are aberrantly expressed in psoriatic tissue can also be directly identified using antibodies directed against them. The psoriatic tissue or an antigenic extract can be used to select an immunoglobulin library. More conveniently, if the practitioner suspects that a particular antigen is aberrantly expressed in the psoriatic tissue, an antibody specific for the antigen and used to test the psoriatic tissue may be provided. Confirmation of overexpression can be obtained, for example, by performing a standard immunoassay on the tissue extract solubilized from the affected tissue, and comparing it with a similar extract from the unaffected tissue. More preferable are immunohistology techniques, using the antibody specific for the suspect target, such as the primary antibody. A suitable determinant, aberrantly expressed, will result in different staining in a section from the affected tissue than from the unaffected tissue, and will also show specificity for the particular cells in the affected sample. An illustration of this is provided in Example 1. Potential candidate antigens include any naturally-occurring ganglioside antigens, antigens that are aberrantly expressed in a spectrum of different cancers, such as CEA, alpha-fetoprotein and gp-72, and antigens that are aberrantly expressed in skin cancers, especially but not limited to melanoma. Melanoma-associated antigens include the gangliosides GM2, GD2, GD3, and their derivatives and analogs; HMW-MAA, MPG, and gp-75. Also of interest are the antigen (T) of Thomsen-Friedenreich (Galßl-3GalNaca-0-Ser), Tn, and sialylated Tn (New5Aca2-6GalNAca-0-Ser). Also of interest is the cell surface marker, CDw60. Suitable glycolipids as target antigens include any of the monosialil-, disialyl- and trisiallyl gangliosides that occur naturally on cells in psoriatic tissue. The preferred target antigens are GM1, GDla, GT1, GT2, and especially GM2, GM3, N-glycolyl-GM3, GDlb, 9-O-acetI1-GD2, GD3, GD3-lactone, 9-0-acetyl-GD3, and GT3.

Types of therapeutic compositions used in this invention Once a suitable target antigen is identified, a composition is designed with a view to recruiting a specific immune response in the subject to be treated against the aberrantly expressed determinant. Any type of composition capable of promoting the specific, desired immune response is adequate. In some embodiments, the invention employs a composition comprising the target antigen, or a modified version, in an immunogenic form. In other embodiments, an effective amount of a composition is employed, wherein an effective amount is an amount sufficient to promote the desired immune response. Accordingly, the antigen is administered in a composition such that an immune response is promoted. For example, the target antigen can be provided by obtaining an enriched fraction from a suitable tissue source or from a suitable cell line, such as keratinocytes, using one of the assays described at the beginning to follow the desired activity. An illustration of this is a vaccine for the sialylated Tn and Tn antigens, which can be prepared from ovine submaxillary gland mucin (O'Boyle et al.). More typically, the target antigen is provided in synthetic form. Where the target antigen is not previously known, it is first characterized by isolation of the antigen complex, or an mRNA that encodes it. Protein antigens can then be prepared by standard peptide synthesis, or by expression of a polynucleotide encoding it in a suitable host cell. The carbohydrate and other non-protein antigens are generally prepared by chemical synthesis, or by a combination of synthetic and isolation techniques. For example, the use of cancer antigens as vaccine preparations is described in BE 1008391 and WO 92/19266 (CEA antigen), and in U.S. Patent No. 5,141,742 (p97 antigen associated with melanoma). Also suitable for use in immunogenic compositions for raising an anti-ganglioside response are the monosiallyl-, disialyl- and trisiallyl ganglioside, together with the synthetic derivatives, including the 9-O-acetyl derivatives, lactone and lactam derivatives and analogs, and episial derivatives; many of which are referred to later in this description. Included in the practice of the invention is the application to psoriasis of ganglioside vaccines and other formulations originally designed for the treatment of cancer or other modalities of clinical care. For example, Helling et al. And Livingston et al. describe GD3 ganglioside, in the form of multiple, synthetic, antigenic peptides, such as conjugates with albumin, KLH, or membrane proteins of Nei seeri a meni? gi ti di s, or as proteosomes. A vaccine to stimulate or increase the production of antibodies against 9-0-acetyl-GD3 is described in U.S. Patent No. 5,102,663. European patent application EP-0443518 describes a cancer vaccine containing episial complex carbohydrates, particularly epiGM3, epiGM4, or epiGM5. European patent application EP-0661061 describes vaccine compositions for promoting an immune response against N-glycosylated gangliosides for the treatment of cancer, particularly N-glycolyl-GM3. Patent application WO 93/10134 discloses ganglioside lactam analogs which are proposed for use in a vaccine for the treatment of cancer. Cheresh et al. describe the biosynthesis and expression of disialoganglioside GD2, a relevant target antigen on small cell lung carcinoma for cytolysis mediated by monoclonal antibodies. PCT patent application WO 94/16731 describes the conjugated ganglioside-KLH vaccines with the adjuvant QS-21, using a ganglioside selected from GM2, GM3, GD2, GD3, GD3-lactone, 0-acetyl-GD3, and GT3. The metabolism of these gangliosides is altered in cancers of neuroectodermal origin, including melanoma (Hamilton et al.). Progenies Pharmaceuticals Inc. is testing a conjugate of GM2-KLH with the adjuvant QS-21 in a Phase III clinical trial in patients with melanoma under the name of the GMK product. A second ganglioside conjugate vaccine, MGV, is also being tested, comprising a combination of 3D2 and GM2 conjugated to KLH. The vaccine is proposed for the therapy not only of melanoma, but also of colorectal cancer, lymphoma, small cell lung cancer, sarcoma, gastric cancer, and neuroblastoma (Progenies Prospectus). Any of these compositions or their active components can be adapted for the treatment of psoriasis according to this invention. Another illustration of a composition suitable for promoting a specific immune response against a target antigen in psoriasis is an anti-idiotype portion. This procedure for immunization arises from Jerne's network theory, which involves a second antibody (Ab2) produced against a first antibody (Abl) which in turn is specific to the target. Ab2 is selected not only for its ability to bind to Abl specifically, but also for its ability to stimulate an additional antibody (Ab3) that cross-reacts with the target. The use of anti-idiotypes in cancer treatment is generally described in U.S. Patent No. 5,053,224. The term "anti-idiotype" or "anti-idiotype portion" as used throughout this application is defined to include not only intact antibody molecules, but any molecules that comprise at least one region or variable portion of a region variable with desired functional properties. The variable region will typically comprise a VH-VL pair, but may alternatively be composed of other combinations of other variables derived from antibodies or T cell receptors. Variable region fragments, fusion molecules, chimeras, and humanized variants they are also included, as long as the required functional properties are preserved. The variable region can be presented in any suitable form, including but not limited to intact antibody molecules, antibody fragments (such as Fab, F (ab ') 2 and Fv), multiple antigenic proteins, and various linker constructs. antigen. Examples of constructs of particular interest include fusion constructs, such as the single chain variable region (scFv) polypeptides, in which a single VH-VL pair is linked through a flexible, peptide linker sequence of one which allows the polypeptide to fold into the three-dimensional conformation of a single variable region. Also included are diabodies, in which two variable regions are linked by a shorter linker that prevents folding in a single variable region, but which allows the chains to dimerize in bivalent molecules with two VH-VL sites. Other constructions of interest include polymeric forms, which contain a plurality (eg, more than one) of polypeptides. The polymeric forms can be linear or branched. The desirable characteristics of an anti-idiotype portion are an ability to bind to an antibody specific for the target antigen (Abl), and the ability to promote an antibody specific for the target antigen, when injected into the subject in question. As used herein, reference to an anti-idiotype for a particular antigen (eg, an anti-idiotype for a ganglioside) means an anti-idiotype that elicits an active immune response specific for the particular antigen in an individual, when it is administered in an immunogenic form. To obtain an anti-idiotype with the desired characteristics, a selection process is employed. A preferred screening method involves the following steps: (1) The positive selection for the antibody (or at least one molecule that has a variable region) capable of binding to the Abl; (2) The negative selection against the antibody that recognizes the isotypic or allotypic determinants of Abl; (3) Positive selection for an ability to inhibit binding of Abl to the target antigen; and (4) Positive selection for an ability to induce a humoral immune response against the target antigen in experimental animals. Typically, the first step involves the multiple immunization of an animal with the Abl, the preparation and cloning of the hybridoma cells from the immune animal, and then testing the cells for the desired specificity on a clone by clone basis. However, other forms for producing or selecting the antibody or antibody equivalents are also suitable. An immunocompetent phage can be constructed to express the segments of the variable region of the immunoglobulin on its surface. See Marks et al., New Engl. J. Med. 335: 730, 1996; International patent applications WO 94/13804, WO 92/01047 and WO 90/02809; and McGuinness et al., Nature Biotechnol. 14: 1149, 1996. The phage of the desired specificity can be selected, for example, by adhesion to Abl coupled to a solid phase, and then amplified in E. col i. Further elaboration of the selection method and its use in the preparation of an anti-idiotype for a ganglioside is provided in International Patent Application WO 96/22373. Of particular interest are monoclonal antibodies (and derivatives with the same immunogenic properties) with the designations 1A7, 4B5 and BEC-2. The antibody 1A7 is an anti-idiotype for ganglioside GD2, and is described in U.S. Patent No. 5,612,030 and in International Patent Application WO 96/22373. This was deposited with the American Collection of Species Collection (ATCC), now located at 10801 University Blvd., Manassas VA 20110-2209, USA, on December 28, 1994, under Accession No. HB 11786. Antibody 4B5 is an anti-idiotype for ganglioside GD2, and is described in U.S. Patent No. 5,653,977, BEC-2 antibody is an anti-idiotype for GD3 ganglioside, and Patent is described of US No. 5,529,922. Also of interest are the anti-GD2 anti-idiotypes of Cheung et al., and the anti-GM3 anti-idiotypes of Yamamoto et al., one of which was recombined by Hastings et al. , as a chimera with the sequences of the human constant region K. Preferably, the anti-idiotype antibody 1A7 (for a functional portion thereof, as described below) is used.1A7 was produced against the anti-GD2 monoclonal antibody designated 14G2a Antibody 1A7 can be pre stopped in different ways. This is most conveniently obtained from the hybridoma deposited with the ATCC under Accession No. HB-11786, or the progeny thereof. For example, the cells can be cultured in a suitable medium, and the spent medium can be used as a source of antibody. Optionally, matrix-coated channels or spheres and cell co-cultures can be included to enhance or enhance the development of antibody-producing cells. For the production of large amounts of antibody, it is generally more convenient to obtain an ascites fluid. The method of producing ascites generally comprises the injection of hybridoma cells into an immunologically clean, histocompatible or immunotolerant mammal, especially a mouse. The mammal is optionally primed for the production of ascites by prior administration of a suitable composition; for example, Pristano. Alternatively, 1A7 can be chemically synthesized in conjunction with standard methods of protein synthesis. A suitable method is the Merrifield technique in solid phase. Automated peptide synthesizers are commercially available, such as those manufactured by Applied Biosystems. Inc. (Foster City, CA). 1A7 can also be obtained by the use of routine recombinant methods such as described in Sambrook et al. (1989). For example, by using the sequences and information provided therein, a polynucleotide encoding either heavy or light chain of 1A7 can be cloned into a suitable expression vector (which contains the control sequences for transcription, such as a promoter). The expression vector is in turn introduced into a host cell. The host cell is developed under suitable conditions such that the polynucleotide is transcribed and translated into a protein. The heavy and light chains of 1A7 can be produced separately, and then combined by rearrangement of disulfide bond. Alternatively, vectors with separate polynucleotides that encode each strand of 1A7, or a vector with a single polynucleotide that codes for both strands as separate transcripts, can be transfected into a single host cell which can then produce and assemble the entire molecule. Preferably, the host cell is a higher eukaryotic cell that can provide the normal carbohydrate complement of the molecule. The 1A7 thus produced in the host cell can be purified using standard techniques known in the art. A polynucleotide encoding 1A7 for use in the production of 1A7 by any of these methods can in turn be obtained from the hybridoma that produces 1A7, or be produced synthetically or recombinantly from the DNA sequence provided in the I presented . Methods of antibody isolation are well known in the art. See, for example, Harlow and Lane (1988) An tibodi is: A Labora t ory Manual, I Cold Spring Harbor Laboratory, New York. The antibody 1A7 is a mouse immunoglobulin of subclass IgGl, and can be isolated by any suitable technique for the immunoglobulins of this isotype. Purification methods may include saline precipitation (for example, with ammonium sulfate), ion exchange chromatography (for example, on a cationic or anionic exchange column run at neutral pH and eluted with incremental gradients of increasing ionic strength). ), gel filtration chromatography (including HPLC gel filtration), and chromatography on affinity resins such as protein A, protein G, hydroxyapatite, and ant i-immunoglobulin. 1A7 can also be purified on affinity columns comprising paratope 14G2a; for example, in the form of a purified Abl or Ab3. Preferably, 1A7 is purified from ascites of BALB / c using protein chromatography A-CL-SEPHAROSEMR 4B followed by chromatography on an ion exchange column DEAE-SEPHAROSEMR 4B. Alternatively, an active portion (see above under the description of 'anti-idiotype' or 'anti-idiotype portion') of 1A7 may be used, which comprise a portion or a complete variable region of 1A7. Examples of variable region constructions (either intact or fragments) have been provided above. Figures 2 and 3 provide the polypeptide sequences in the light and heavy chain variable regions, as well as the polynucleotide sequences encoding the variable regions. The preparation of these 1A7 polypeptides employs standard techniques, such as recombinant techniques, known in the art. The 1A7 polypeptides can be produced by proteolytic or other degradation of 1A7, by recombinant methods (e.g., single or fusion polypeptides) as described above or by chemical synthesis. The 1A7 polypeptides, especially shorter polypeptides of up to about 50 amino acids, are conveniently made by chemical synthesis. Chemical synthesis methods are known in the art and are commercially available. For example, a 1A7 polypeptide could be produced by an automated polypeptide synthesizer using the solid phase method. Preferably, the polypeptides are at least partially purified from other cellular constituents. Preferably, the polypeptides are at least 50% pure. In this context, the purity is calculated as a percentage by weight of the total protein content of the preparation. More preferably, the proteins are 50-75% pure. The most highly purified polypeptides can also be obtained and are encompassed by the present invention. For clinical use, the polypeptides are preferably highly purified, at least about 80% pure, and free of pyrogens and other contaminants. Protein purification methods are known in the art and are not described in detail herein. Alternatively, if one or more 1A7 polypeptides are expressed in a suitable storage medium, such as a plant seed, the 1A7 polypeptide does not need to be purified and could even be administered without purification. Fiedler et al. (1995) Biotechnology 13: 1090-1093. The 1A7 polypeptides can be obtained from intact 1A7, which can in turn be isolated from hybridoma ATCC Accession No. HB-11786 which produces 1A7, which is described in U.S. Patent No. 5,612,030 of common membership and the International patent application WO 96/22373. The techniques of isolating antibodies from hybridomas are well known in the art. See, for example, Harlow and Lane (1988). Once intact 1A7 is obtained, 1A7 polypeptides can be obtained by intact 1A7 degradation, through the use, for example, of proteolytic enzymes (proteinases). Examples of proteolytic enzymes include, but are not limited to trypsin, plasmin, and thrombin. The intact 1A7 can be incubated with one or more proteinases, or the digestions can be performed sequentially. The nature and degree of proteolytic cleavage will depend on the desired polypeptide length as well as on the enzymes used. These techniques are well known in the art. Alternatively, or in addition, the intact 1A7 can be treated with reducing agents of the disulfide bond to dissociate the molecule. The 1A7 polypeptides can also be made by chemical synthesis using techniques known in the art. The 1A7 polypeptides can also be made by expression systems, using recombinant methods. The availability of the 1A7 polynucleotides encoding the 1A7 polypeptides allows the construction of expression vectors encoding intact 1A7, functionally equivalent fragments thereof, or recombinant forms of 1A7. A polynucleotide encoding the desired 1A7 polypeptide, either in a fused or mature form, and containing or not a signal sequence to allow secretion, can be ligated into suitable expression vectors for any convenient host. Eukaryotic and prokaryotic host systems can be used. The polypeptide is then isolated from lysed cells or from the culture medium and purified to the extent necessary for its intended use. The purification or isolation of the polypeptides expressed in the host systems can be achieved by any method known in the art. By 4% example, cDNA encoding intact 1A7 or a fragment thereof, can be operably linked to a suitable promoter, inserted into an expression vector, and transfected into a suitable host cell. The host cell is then cultured under conditions that allow transcription and translation to occur, and the desired polypeptide is recovered. Other segments that control transcription or translation, such as signal sequences that direct the polypeptide into a specific cell compartment (eg, for secretion), may also be used. Examples of prokaryotic host cells are known in the art and include, for example, E. coli. Examples of eukaryotic host cells are known in the art and include yeast, poultry, insect, vegetable, and animal cells such as C0S7, HeLa, CHO and other mammalian cells. For the scFv fragments, the light and / or heavy chain variable regions are linked using a short binding peptide. Bird et al. (1998) Science 242: 423-426. An example of a binding peptide is (GGGGS) 3, which bridges approximately 3.5 nanometers between the carboxyl terminus of a variable region and the amino terminus of the other variable region. The linkers of other sequences have been designated and used. Bird et • al. (1988). Usually the linkers are selected to have little to no immunogenicity. For asymmetric linkers, the scFvs can be assembled in any order. In general, the complete variable regions are included in the scFv, which can be produced either recombinantly or synthetically. Yet another illustration of a composition suitable for promoting a specific immune response against a target antigen in psoriasis is an expression vector encoding a polypeptide that is used in an immunogenic composition. The polypeptide encoded by the vector is either one comprising the antigenic determinant that is aberrantly expressed in the psoriatic tissue, or even an anti-idiotype for the aberrantly expressed determinant. The coding region is linked in the vector to the appropriate transcription and translation control elements that allow the coding region to be expressed in the intended subject, after administration.

Vaccines made of naked polynucleotides are generally described in Tang et al. (1992) Nature 356: 152-154. Viral vectors are also suitable, including by way of example, vectors based on herpesviruses, hepadnaviruses, Sindbis virus, retroviral vectors of pseudotype, adenovirus, adeno-associated virus. Where the coding region codes for an anti-idiotype, of particular interest are the vaccinia virus-based vectors that can be used in vaccine preparations (Moss (1991) Science 252: 1662-1667). Such vectors can be constructed, for example, by homologous recombination of vaccinia plasmids and wild-type strain WR of vaccinia virus using CV-1 cells, according to the method of Mackett et al. (DNA Cloning, Vol. II, D.M. Glover, ed., IRL Press 1985).

Formulation of therapeutic compositions The preparation of the pharmaceutical compositions is conducted in accordance with generally accepted procedures for the preparation of pharmaceutical preparations. See, for example, Remington's Pharmaceuti cal Sci ences 18a Edi cion (1990), E.W. Martin ed., Mack Publishing Co. , PA. Depending on the intended use and mode of administration, processing optionally includes sterilization, mixing with appropriate non-toxic and non-interfering components, division into dosage units, or enclosure in a delivery device. The protein vaccines used in this invention typically comprise an adjuvant, which may be the same as or in addition to the excipient or carrier. Examples of adjuvants include, but are not limited to aluminum hydroxide, alum, QS-21 '(U.S. Patent No. 5,057,540), DHEA (U.S. Patent Nos. 5,407,684 and 5,077,284) including its precursors and modified forms (e.g., DHEA-S, the sulfonated form of DHEA), β2 microglobulin (WO 91/16924), muramyl-dipeptides, muramyl-tripeptides (U.S. Patent No. 5,171,568), monophosphoryl lipid A ( Patent of the United States No. 4,436,728; WO 92/16231) and its derivatives, such as various forms and generations of DETOXMR and BCG (U.S. Patent No. 4,726,947). Other suitable adjuvants are aluminum salts, mixtures of squalene (SAF-1), muramyl-peptide, saponin derivatives, mycobacterial wall preparations, icolic acid derivatives, non-ionic block copolymer surfactants, Quil A, B subunit of the toxin. of cholera, polyphosphazene and derivatives, and immunostimulatory complexes (ISCOMs) such as those described by Takahashi et al. (1990) Nature 344: 873-875. For veterinary use and for the production of antibodies in animals, complete and incomplete Freund's adjuvant can be used. A preferred vaccine composition for peptides and anti-idiotypes or peptide derivatives thereof, is prepared by mixing with aluminum hydroxide and incubated at about 48 ° C for about 30 minutes. Especially preferred adjuvants include QS-21 and RIBIMR PC. The QS-21 molecule consists of a triterpene glycoside with the general structure of a 3, 28-O-bis-glucoside of the chelating acid. There are two structural isomers designated V-1 and 2-1 at a typical ratio of 2: 1, which have adjuvant activity. QS-21 has been shown to stimulate a response against T cell-dependent antigens and non-conjugated T-cell independent antigens. QS-21 also increases the induction of MHC Class I cytotoxic T lymphocytes to subunit antigen vaccines, as well as antigen-specific cell proliferation. The preclinical tests confirm its safety and efficacy at 100 μg / dose. C5-21 is administered by Aquila Biopharmaceutical, Inc. in Worchester, MA. The composition may also optionally contain other active medicinal agents, and / or non-active ingredients such as carriers, and auxiliary substances such as wetting or emulsifying agents, and pH-buffering agents. The additives of particular interest are adjuncts that enhance the immunogenic effect, such as mitogens or stimulatory cytokines. Of particular interest as adjunct agents for the anti-idiotype compositions are interleukins, particularly IL-2. The composition is typically formulated in liquid form, but can also be lyophilized for reconstitution by hydration. The administration route is selected according to the formulation of the composition and the intended effect. In the most usual embodiments of this invention, the composition is formulated and administered to stimulate a systemic response in the subject. With this in view, possible routes of administration include intracutaneous, subcutaneous, intramuscular, intraperitoneal, intradermal, oral, intranasal, intradermal, and intrapulmonary (e.g., aerosol) routes. The protein vaccines of this invention for human use are typically administered by a parenteral route, more preferably subcutaneously. A series of injections is preferably administered at different subcutaneous sites. In other embodiments, the composition is formulated and administered to produce a local effect (eg, it is formulated for topical administration). These compositions are generally used to trigger at an affected site a response in an individual, where a systemic immune response against the target antigen has already been successfully induced, although pre-generation of a systemic immune response is not required. In these embodiments, the composition is generally in the form of a cream or gel, or other combination of the active ingredient and a readily absorbable or evaporable excipient. The composition is then administered on the skin at the affected site. Accordingly, the invention provides topical formulations of any target antigen (antigenic determinants) described herein, such as gangliosides., anti-idiotype portions (eg, anti-idiotype portions, including anti-idiotype antibodies, for any of the gangliosides described herein), and the expression vectors described herein. Preferably, a topical formulation comprises 1A7. Examples of suitable topical formulations, which are well known in the art, include ointments, creams, and gels. In certain embodiments of the invention, the composition is specially designed for psoriasis, comprising a formulation and dosage that is specially designed to maximize the management of the psoriatic condition. In other embodiments, the composition is formulated in a similar manner as it might be for use in another type of therapy, such as for the treatment of cancer, which shares a common goal, such as promoting an immune response against an antigen that it is aberrantly expressed in any condition. Preferably, compositions useful for the treatment of psoriasis according to the present invention are accompanied by written instructions as part of the package or in a product insert. The written instructions may simply indicate that psoriasis (in any of its many forms) is an adequate indication for the use of the composition. Optimally, the instructions will also indicate the subjects and the appropriate conditions, the recommended route of administration, the synchronization in time, and the dosage, the contraindications, the potential side effects, and the expected benefit. The invention accordingly provides a composition for the use (or the use of any of the composition or compositions described herein) in the preparation of a medicament for use in the treatment of psoriasis. These compositions comprise any of the embodiments described herein. In one embodiment, the invention provides the use of a component selected from the group consisting of i) a ganglioside; ii) an anti-idiotype portion for a ganglioside; and iii) an expression vector encoding an anti-idiotype for a ganglioside in the manufacture of a medicament for the treatment of psoriasis. The psoriasis to be treated can be any of the psoriasis due to glutathione, pustular psoriasis, plaque type psoriasis, psoriatic arthritis, and / or chronic plaque psoriasis. The ganglioside can be any of GM2, GM3, GD1B, GD2, 9-0-acetyl-GD2, GD3, GD3-lactone, 9-0-acetyl-GD3 and GT3. The anti-idiotype portion may be any of 1A7, 4B5 or BEC-2, and is preferably 1A7.

Use of therapeutic compositions Suitable patients for treatment according to this invention have clinical or histological features of psoriasis, particularly psoriasis by glutathione, pustular psoriasis, plaque-type psoriasis, or psoriatic arthritis. The compositions may also be administered to patients who have no external signs of psoriasis, but are at risk of developing the disease especially in its most severe manifestations (due to a genetic predisposition, family history or previous manifestations), although this is less typical. Since the effectiveness of this invention is believed to involve a host immune response against the target antigen, the therapeutic compositions are predicted to be most effective when the individual is not immunodeficient or immunocompromised due to a genetic abnormality, infection, or by treatment with chemical products . The amount of the immunogenic substance administered at one time is selected for clinical safety, and to achieve the desired immunological and clinical result, initial within a few administrations. The range of effective concentrations for protein immunogens is generally from about 10 μg to 20 mg, and typically from 200 μg to 10 mg, with the tendency towards higher values where the. Immunogenic determinant is a proportionally smaller part of the protein. The range of effective concentrations for polynucleotide vaccines is generally about 10 μg to 500 μg of nucleic acid, typically about 50 to 100 μg. Since it is believed that clinical efficacy correlates with the degree of specific immunological response obtained, a dose that is clinically effective can in principle be predicted by determining an immunogenic dose in an animal model, and then elevating the dose appropriately to human use Administrations are typically conducted on a weekly or biweekly basis until there is evidence of an immunological or clinical response. The administration can then be continued on a less frequent basis, such as biweekly, monthly, or bi-monthly, as appropriate. Treatment according to this description may optionally be combined with other regimens focused on clinical symptoms, including but not limited to local treatment with topical steroids, topical calcipotriol, or ultraviolet light; or systemic treatment with methotrexate, etretinate or cyclosporine. The parallel treatment may also be conducted with a view to activating the immune system to make it more responsive to the vaccine, such as the simultaneous administration of a mitogen or cytokine. In one example, IL-2 is injected into a collateral site at a dose of approximately 1.5 to 15 x 106 U m ~ 2 day-1, either throughout the preparation or priming phase of the vaccine treatment, or as a pulse given a few consecutive days in a biweekly scheme, or any reasonable variation. The clinical response is measured with respect to the time of administration and regular follow-up. The immune response can also be measured, if desired, by collecting periodic blood samples for analysis. The presence of the activity of the antibody (for example, against a particular ganglioside or a particular anti-idiotype) can be determined by standard immunoassay of serum or plasma samples from the treated subject. For the anti-idiotype activity, the sample is pre-incubated with autologous immunoglobulin or adsorbed on a suitable affinity resin to eliminate the activity of the antibody, against the isotypic and allotypic determinants. In a test method, the sample is incubated in a well of microtitre plate previously coated with the target antigen; the well is washed, and then the reaction is revealed with an anti-immunoglobulin reagent labeled isotopically or enzymatically. The results are compared with those using pre-immune serum or serum from subjects immunized with an unrelated antigen. The specificity can also be measured by staining or Western blotting. The antigen is separated by electrophoresis on a polyacrylamide gel, transferred over nitrocellulose, and then developed with the sample. In a third example, the sample is incubated with cells that express or not the antigen of interest, and then developed using a fluorescently labeled anti-immunoglobulin. The frequency and intensity of staining can then be measured by FACS analysis. A model cell line is one that expresses GD2 and is M21 / P6. In a fourth example, the sample is extended over a histological sample from a psoriatic lesion, as it can be taken from the treated subject, and then revealed with the enzyme-labeled anti-immunoglobulin. This is illustrated in Example 3. The nature of the response in the sample can be further characterized in any of these assays by competition with an antibody with known activity for the target antigen. A model antibody for GD2 is the monoclonal antibody 14G2a. Complement mediated cytotoxicity (CMC) can be measured, if desired, using a cell line that expresses the target antigen. The cell line is labeled with a cytosolic marker, such as 51Cr. The assay is conducted by the addition and incubation of a sample suspected of containing antibody. The supplement is added in a suitable form, such as guinea pig serum pre-adsorbed with the cell line. After a suitable incubation period at 37 ° C, the degree of 51 Cr release is measured and compared with that of non-opsonized control cells. Target cells labeled with 51 Cr can also be used to measure the antibody-mediated cytotoxicity, antibody dependent (ADCC) in the sample, by the delivery of human peripheral blood mononuclear cells (PBMC) from normal subjects, such as cells effector to a proportion of effector cells: target of approximately 100: 1. A cell-mediated immune response in a subject can be measured by isolating PBMC from a blood sample of the treated subject, collected in heparinized tubes, and separated over a suitable gradient such as Ficoll-Hypaque ™. To measure the proliferation of T cells (a general indicator of the activation of T cells against the antigen), the cells are incubated with a range of concentrations of the target antigen. A non-specific mitogen such as PHA serves as a positive control; incubation with an unrelated antigen serves as a negative control. After incubation of the PBMCs for an appropriate period (typically 5 days), the incorporation of [3 H] thymidine is measured, and the proliferating cells can further be characterized by flow cytometry using specific markers of the cell type. The response of cytotoxic T cells can be measured after a period of stimulation by presentation with the target cells that possess the 51 Cr-labeled antigen. The clinical result is followed in the course of therapy for a therapeutic effect and the undesirable side effects, as illustrated in Example 4. Ideally, the compositions promote the resolution of the clinical features, but the stabilization of the condition is a result satisfactory. The progression or regression of the disease is followed according to the particular clinical manifestations of the original presentation, and typically includes the number and size of psoriatic lesions, and the degree of the total surface area of the body that is involved. The condition can also be measured at the microscopic level as the ratio of the proliferation of epidermal cells or the proportion of cells expressing the target antigen.

The selection of the target antigen (or the antigenic determinant) and the composition of the immunogenic formulation can be adjusted by the manufacturer, and the exact dose and timing for administration can be adjusted by the attending physician, without departing from the spirit of the invention. The invention also provides methods for preparing a composition for use in the treatment of psoriasis, comprising producing an anti-idiotype antibody against a monoclonal antibody that binds to an antigenic determinant that is aberrantly expressed in psoriatic tissue, in wherein the anti-idiotype antibody is capable of promoting an immune response in a human against the antigenic determinant. Alternatively, the methods comprise the preparation of an immunogenic composition comprising the aberrantly expressed determinant.

Selection methods of the invention The invention also provides methods for the selection of immunogenic compositions for use in the treatment of psoriasis in humans. In some embodiments, the methods comprise the steps of (a) administering to a plurality of human subjects having psoriasis, an immunogenic composition comprising an immunogenic form of i) an antigenic determinant that is aberrantly expressed in psoriatic tissue; ii) an anti-idiotype monoclonal antibody for an antigenic determinant that is overexpressed in psoriatic tissue; or iii) an expression vector encoding either i) or ii); and (b) the correlation of the progression of psoriasis in the human subjects treated in step (a) in relation to that in the untreated human subjects having psoriasis, with the effectiveness of the immunogenic composition. In other embodiments, screening methods comprise the following steps: a) administration, to a plurality of human subjects having psoriasis, of an immunogenic composition comprising an immunogenic form of: i) an antigenic determinant that is aberrantly expressed in the psoriatic tissue; ii) an anti-idiotype antibody, monoclonal, for an antigenic determinant that is aberrantly expressed in psoriatic tissue; or iii) an expression vector encoding either i) or ii); and b) determining the degree of an immunological response against the antigenic determinant in each subject treated in step a); and c) the correlation of the progression of psoriasis in relation to the degree of immunological response against the antigenic determinant in each subject, with the effectiveness of the immunogenic composition. In any of these selection modalities, the antigen that is aberrantly expressed in the psoriatic tissue may preferably be a ganglioside, more preferably GD2.

Equipment of the invention The invention also provides the equipment comprising a) a composition packaged in a container and comprising an immunogenic form of a component selected from the group consisting of: i) a ganglioside; ii) an anti-idiotype for a ganglioside; and iii) an expression vector that codes for an anti-idiotype for a ganglioside; and b) written instructions for the use of the composition in the treatment of psoriasis. Preferably, the components is 1A7. The examples presented below are provided as an additional guide for a practitioner of ordinary skill in the art, and are not intended to be limiting in any way.

EXAMPLES Example 1: Demonstration of ganglioside antigen in psoriatic tissue In this experiment, the histological sections of psoriatic lesions were selected for the presence of aberrantly expressed antigens, which could be suitable targets for an active vaccination strategy. Skin biopsies were obtained from patients who had Derma ti ti s Psori thus benign. Paraffin blocks from three samples were cut into 5 μm cross sections through the dermal layers. Sections were fixed on slides and deparaffinized by a series of graduated washes of decreasing ethanol content. Once balanced in the phosphate buffered saline solution, pH 7.4, the sections were blocked against the non-specific binding by extension with 10% normal rabbit serum that had been inactivated by heat. After washing, the sections were spread on a panel of purified primary antibodies by anion exchange chromatography, as required, and diluted to 50 μg / ml. The section was incubated with the primary antibody at room temperature for approximately 1 hour, and then washed again. The section was then extended with rabbit anti-mouse immunoglobulin, biotinylated, as the secondary antibody, incubated and washed. The sections were developed using a streptavidin-peroxidase conjugate, followed by the substrate. The panel of the primary antibodies consisted of the following: • The 14G2a monoclonal antibody, developed from a hybridoma cell line obtained from the Scripps Research Institution. 14G2a has been subtyped as an IgG2a ?. 14G2a is specific for the ganglioside antigen GD2, and does not bind to the gangliosides GM1, GM2, GM3, GD3 or GTlb. The ability of 14G2a to bind to GD2 in fixed tissue was confirmed by immunoperoxidase staining of paraffin blocks of human melanoma tissue. 14G2a also binds specifically to the M21 / P6 melanoma cell line positive to GD2, when it is used as the primary antibody in the FACS analysis. • Monoclonal antibody 8019, produced from the hybridoma obtained from the North American Species Culture Collection (ATCC, Rockville MD). 8019 has been subtyped as an IgGl ?, and is specific for the carcinoembryonic antigen (CEA). The ability of 8019 to bind to CEA in fixed tissue was confirmed by immunoperoxidase staining of paraffin blocks from human colon cancer samples. 8019 also binds specifically to the LS174-T colon cancer cell line positive for CEA, when used as the primary antibody in the FACS analysis. • The MC-10 monoclonal antibody, also designated BrE-1, is specific for the human milk fat globule (HMFG), an antigen aberrantly expressed in breast carcinoma cells. MC-10 has been subtyped as an IgG2b ?. The ability of MC-10 to bind to HMFG in sections of fixed tissue was confirmed by immunoperoxidase staining of the paraffin blocks of human breast cancer samples. MC-10 also specifically binds MCF-7 and SKBR3 breast cancer cell lines positive to HMFG, when used as the primary antibody in the FACS analysis. • A mouse monoclonal IgG2b of unknown specificity, purchased from Sigma Chemical Co. , it serves as a negative control.

The staining intensity was rated on a scale from (-) to (++++). The following results were obtained: Antibodies 14G2a and 8019 gave strong staining in all samples tested. The staining pattern was consistent with the specific staining for the affected tissue, since only the dermal layers were stained. The monoclonal antibody MC10 was essentially negative. These results indicate that GD2 and CEA are candidate targets for a vaccine strategy against psoriasis.

Example 2: Promotion of an anti-GD2 response in humans using an anti-idiotype Hybridoma cells expressing the anti-idiotype monoclonal antibody 1A7 (U.S. Patent No. 5,612,030) were used for the production of ascites fluid. 9.7 g of the purified antibody were prepared by TSD Bioservices under GMP conditions (good manufacturing practices). Regulatory tests on antibody preparation were completed according to FDA guidelines. This example describes how the antibody is tested in a human clinical study to verify safety and demonstrate its ability to promote an anti-GD2 response in humans. Patients are immunized with the antibody 1A7 mixed with 100 μg of the adjuvant QS-21. patients are randomized to one of the four dose levels. The total number of patients is between approximately 12 and 32. Injections are administered biweekly for four total doses, or until an immune response is observed. The therapy continues with monthly injections until tumor progression is found. Patients are periodically checked carefully for anaphylaxis, serum sickness, and other potential side effects. Periodic blood samples are obtained to determine the effect on hematopoietic cells as well as renal and hepatic function. All patients admitted to the study suffer from leukapheresis before the first immunization (pre-therapy). In addition, blood samples are obtained before each injection of 1A7 to determine serum levels of Ab3 and Ab1 'antibodies and cytotoxic T cell responses. The specificity of humoral responses is confirmed by immune flow cytometry, radioimmunoassay, and dot blot analysis. The antiglobulin responses to the murine antibody are tested by sandwich radioimmunoassay. The sera are also tested for the ability to inhibit the binding of the anti-GD2 mAb to the GD2 antigen. The immune profile of the patients is further evaluated by testing the proliferative response of the patient's lymphocytes to the anti-idiotype antibody, the purified GD2 antigen, and the irradiated tumor cells and the cytotoxicity of the patient's lymphocytes for the corresponding cell lines to HLA, positive to GD2 or autologous tumor cells (where possible). What follows are the results of seven participants in the study in a period sufficient to evaluate the presence of an immune response. Each patient was immunized with 1 mg, 2 mg, 4 mg, or 8 mg of antibody 1A7 in QS-21 in a biweekly scheme. For the first few patients in the study, the first 2 to 4 doses were administered intramuscularly, and periodic serum samples were collected to determine the presence of human anti-mouse activity (HAMA) and anti-Ia7 activity. Titers were low, and it was decided to continue the course of immunization subcutaneously. All patients were seroconverted as positive with respect to HAMA and anti-Ia7, as determined by the immunoassay. The response comprised the specific activity of Ab3, as demonstrated by the ability of each serum to inhibit the binding of radiolabeled 1A7 to 14G2a (Abl) linked to the solid phase. None of the patients has yet shown objective clinical responses related to their cancer. Nevertheless, three of the seven patients (days 270+ to 510+) have stable disease and continue on the vaccine therapy. The results demonstrate that administration of 1A7 as a pharmaceutical composition with adjuvant QS-21 is very well tolerated up to a dose of 8 mg, and is highly effective in generating an anti-GD2 response. To investigate the nature of the additional response, the anti-IAA antibody was purified by affinity from the sera of four of the patients. First, each sample was passed over a 14G2a antibody column, eluted with a glycine buffer (pH about 2.5), and exchanged in PBS. Next, the HAMA activity that was not Ab3 was depleted by negative selection on a mouse immunoglobulin adsorbent. The amount of the specific anti-lA7 (Ab3) obtained was as follows: Patient 1 (administered 1 mg of 1A7 per dose), yield 0.67 mg of Ab3 from 10 ml of serum. Patient 2 (was administered 2 mg of 1A7 per dose), yield 1.32 mg of Ab3 from 10 ml of serum. Patient 3 (was administered 4 mg of 1A7 per dose), yield 1.71 mg of Ab3 from 10 ml of serum. Patient 4 (was administered 4 mg of 1A7 per dose), yield 0.73 mg of Ab3 from 10 ml of serum. This indicates that a substantial amount of Ab3 is produced as a result of the administration of 1A7 at any of the doses tested, and apparently is in molar excess of the antigen in the circulation. The affinity and specificity of the response to GD2 was further confirmed by the use of affinity purified Ab3 in several of the test systems described at the beginning. In one test, a test plate was coated with ganglioside GD2 or GD3, covered with purified Ab3, and then developed with anti-immunoglobulin labeled with alkaline phosphatase. The results showed that each patient response comprises the production of the anti-GD2 antibody (Ab1 ') but not the anti-GD3 antibody. In yet another test, a test plate was coated with GD2, coated with purified Ab3, and then developed with the isotype-specific anti-immunoglobulin reagents. The anti-GD2 response was apparently a mature response comprising IgG and IgM, with the predominant IgG. The inhibition titration experiments were conducted using the purified Ab3 from three different patients. In one test, a test plate was coated with ganglioside GD2, and varying amounts of purified Ab3 were tested for the ability to inhibit radiolabelled 14G2a binding (Abl). The average titration point for each Ab3 was comparable to that of the unlabelled 14G2a. In yet another test, varying amounts of the purified Ab3 were tested for their ability to inhibit the binding of radiolabeled 14G2a to the line of murine EL4 lymphoma cells expressing GD2. the results indicated that the Ab3 induced by administration of 1A7 competes for the aberrantly expressed GD2 binding by the model target cells.

EXAMPLE 3 Demonstration of the antibody for the antigen associated with psoriasis in the serum of immunized human subjects The affinity of purified Ab3 from the sera of human patients treated with an anti-idiotype was tested for the presence of the circulating antibody against an antigen associated with psoriasis.

Patients were treated with monoclonal anti-idiotype 1A7 (an anti-idiotype for GD2), or with anti-idiotype 3H1 (an anti-idiotype for CEA). The treatment of subjects with 1A7 is described in Example 2. The preparation and use of 3H1 is described in PCT patent applications WO 96/20219 and WO 96/20277. After a course of multiple immunizations in a biweekly immunization schedule, the respective Ab3 present were prepared by passing immune sera over an elaborate affinity column of the immunization antibody, and recovering the bound fraction. As a negative control, normal or preimmune human IgG was prepared by passing serum from a non-immunized subject onto a G protein column. The purified IgG fractions were then tested for their ability to specifically stain the affected psoriatic tissue, using the methods Tochemical immunohistodes described in Example 1. The results are shown in the following Table: The results show that the treatment of human patients with the monoclonal antibody 1A7 successfully promotes an active immune response that is specific for a target antigen on the affected psoriatic tissue. The target antigen is shared between different patients with psoriasis and (in view of the known immunogenic properties of the 1A7 antibody) it is most likely GD2. The specificity is confirmed by two additional observations: a) the staining pattern with Ab3 from the subject treated with 1A7, showed the staining of the cells affected of the skin but not the surrounding muscle fibers; b) the anti-idiotype antibody 3H1 promotes a specific response of Ab3, but the response was apparently non-specific for the tissue with psoriasis.

Example 4: Treatment of psoriasis by promoting an active anti-ganglioside immune response Psoriasis affects approximately 1 to 2 percent of the adult population in various forms. Patients with extensive plaque psoriasis and pustular psoriasis frequently require systemic therapy. Topical steroids, topical calcipotriol, or ultraviolet light may not give adequate control. Currently used systemic medications such as methotrexate, etretinate and cyclosporin are sometimes effective, but associated with significant side effects. A patient with advanced psoriasis was administered monoclonal antibody 1A7 as part of a clinical trial for the treatment of melanoma. After leaving the test, the patient returned to the attending physician (Dr. K. Foon) and reported that his psoriatic symptoms, which had previously been persistent, had improved. Their case history and immunological test results were reviewed, and it was found that the resolution of symptoms correlated with the stimulation of an anti-GD2 immune response (as detected in the serum) during the 1A7 treatment in the test of melanoma. Subsequently, tissue samples with psoriasis from several patients were evaluated by immunohistochemistry (Example 1), and all were positive for an antigen recognized by the anti-GD2 antibody. The antibody present in the serum of several patients immunized with the anti-idiotype of GD2, 1A7, was isolated, and was found to react with a target antigen on the psoriatic tissue (Example 3). This example provides a method to test the efficiency of raising or promoting an anti-GD2 immune response in the treatment of psoriasis. Fifteen patients who had been diagnosed with severe chronic plaque psoriasis and who had an unsatisfactory response to previous systemic therapy, topical steroids or ultraviolet light were treated. The criteria of choice also include the absence of active infection or blood borne disease, adequate renal and hepatic function tests, granulocyte count >; 1000 mm "3, platelets> 100,000 mm" 3, absence of allergy to mouse protein, and ability to provide informed consent. The subjects are preselected for the presence of the GD2 antigen on keratinocytes in psoriatic lesions by immunohistology, as exemplified in Example 1. Figure 1 shows the treatment scheme. Admitted patients are treated with 2 mg of 1A7, mixed with 100 μg of adjuvant QS-21. Four injections are given initially, one every third week, and then the injections are given monthly. Treatment is stopped if there is a significant adverse event, if there is substantial progress of the disease, or if there is no significant effect after six months. Patients who show progression of the disease are followed for an additional six months after cessation of treatment. Patients with stable or improved disease six months after the start of treatment receive additional treatment for an additional six months, followed by another evaluation. During the course of the test, patients are periodically checked for toxicity. Periodic blood samples are taken to determine any effect on hematopoietic cells, renal and hepatic function, LDH and uric acid. The most likely side effects are local skin reaction, fever, chills, and sweating, sometimes requiring therapy and persisting only for a few hours. Anti-pruritics are used where necessary. Allergic reactions are treated symptomatically with diphenhydramine or hydroxyzine. Bronchospasm and anaphylaxis, if they occur, are treated with epinephrine and supportive care, and result in the patient's withdrawal from the treatment regimen. In view of the previous 1A7 tests in patients with cancer (Example 2), no major toxicity is anticipated. Periodic blood samples are also taken to monitor the immune response in each patient. The presence of antibodies against 1A7 (the response of Ab3) and against GD2 (the response of Abl ') is measured by standard immunoassay of plate binding. Serum or isolated Ab3 is also tested for binding to GD2 expressed on tumor cell lines or psoriatic tissue. The cell-dependent cytotoxicity of the antibody, the proliferative activity of T cells, or the activity of cytotoxic T cells can also be measured according to the procedures described elsewhere in this description. The induction of humoral and cellular anti-GD2 activity is anticipated in most treated subjects after four or more injections with the 1A7 vaccine. The results are determined as follows. The symptoms are rated according to the Psoriasis Area and the Severity Index. The severity is rated on a numerical scale (0 = none, 1 = light, 2 = moderate, 3 = severe), taking into account erythema, scaling and induration. The degree or extension is based on the involvement of the total area of the body (trunk = 35%, legs = 35%, arms = 20%, head and neck = 10%). The progression is then rated between -1 and +3 (-1 = worse, 0 = stable, +1 = minimum improvement, +2 = defined improvement, +3 = elimination). The clinical experience is that without treatment the disease will progress typically, involving more surface or having plaque with more erythema and induration. Treatment is considered successful if there is substantial improvement or stabilization of the disease, compared to the typical course in patients not treated with the vaccine, and who initially present similar symptoms and clinical experience. Although the above invention has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be apparent to those of skill in the art that certain changes and modifications will be practiced. Therefore, the description and examples should not be considered as limiting the scope of the invention, which is delineated by the appended claims.

Non-exhaustive list of cited references 1. Beardsley T. Crabshoot. Manufacturers gamble on cancer vaccines - again. Scientific American p. 102, Sept. 1994. 2. Bhattacharya-Chatterj ee, M. et al. Idiotype vaccines against human T cell acute lymphoblastic leukemia. I. Generation and characterization of biologically active monoclonal anti-idiotypes. J. Immunol. 139: 1354-1360, 1987. Chattopadhyay P. et al. Murine monoclonal anti-idiotype antibody breaks unresponsiveness and induces a specific antibody response to human melanoma-associated proteoglycan antigen in cynomolgus monkeys. Proc. Natl. Acad. Sci. USA 89: 2684-2688, 1992. Cheresh, D.A. et al. Biosynthesis and expression of the disialoganglioside GD2, a relevant target antigen on small cell lung carcinoma for monoclonal ant ibody-mediated cytolysis. Cancer Res. 46: 5412-5118, 1996. Cheung, N-K.V. et al. Ganglioside GD2 specific monoclonal antibody 3F8. A Phase I study in patients with neuroblastoma and malignant melanoma. J. Clin. Oncol. 5: 1430-1440, 1987. Cheung, N.-K.V. Cañete, A. Cheung, I. Y. Ye, J.-N. and Liu, C. Disialoganglioside GD2 anti-idiotypic monoclonal antibodies. Int. J. Cancer 54: 499-505, 1993. Conry RM et al. A carcinoembryonic antigen polynucleotide vaccine for human clinical use. Cancer Gene Ther. 2: 33-38, 1995.

Denton G.W. et al. Clinical outcome of colorectal cancer patients treated with human monoclonal anti-idiotypic antibodies. Int. J.

Cancer 57: 10-14, 1994. Hamilton W.B. et al. Gangliosides expression on human malignant melanoma assessed by quantitative immune thin layer chromatography.

Int. J. Cancer 53: 1 ff. 1993. Hastings, A. Morrison S.L. Kanada S. Saxton, RE. and Irie, R.F. Production and characterization of a murine / human chimeric anti-idiotype antibody that mimics ganglioside.

Cancer REs. 52: 1681-1686, 1992. Hawkins, R.E. et al. A genetic approach to idiotypic vaccination. J. Immunother. 14: 273-278, 193. Heindenheim M. Et al. CDw60, which identifies the acetylated form of GD3 gangliosides, is strongly expressed in human basal cell carcinoma. Br. J. Dermatol. 133: 392, 1995. Herlyn D et al. Cloned antigens and anti-idiotypes. Hybridoma 14: 159-166, 1995. Liang P. et al. Differential display of eukariotic messenger RNA by means of the polymerase chain reaction. Science 257: 967-971, 1992. 15. Liang P. et al. Recent advances in differential display. Curr. Opin. Immunol. 7: 274-280, 1995. 16. Livingston, P.O. Construction of cancer vaccines with carbohydrate and protein (peptide) tumor antigens. Curr. Opin. Immunol. 4: 624-629, 1992. 17. Livingston, P.O. Approaches to augmenting the immunogenecy ty of ganglioside melanoma: From whole melanoma cells to ganglioside-KLH conjugate vaccines. Immunol. Review, 145: 147-166, 1995. 18. Mittelman A. Et al. Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse ant i-idiotypic monoclonal antibody MK2-23: Induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proc. Natl. Acad. Sci. USA 89: 466-470, 1992. 19. O'Boyle K.P., Zamore R., Adluri S., Cohen A., Kemeny N., Welt S-, Lloyd K.O., Oettgen H.F., Old L. J., and Livingston P.O. Immunization of colorectal cancer patients with modified ovine submaxillary gland mucin and adjuvants induces IgM and IgG antibodies to sialylated Tn. Cancer Res. 1992. (REference 17 of Livingston, 1992). Offner H. Et al. Lymphocyte stimulation by gangliosides, cerebrosides and bsic protein in juvenile rheumatoid arthritis. J. Clin. Lab. Immunol. 6. "35-37, 1981. Paller AS et al., Absence of a stratum corneum antigen in disorders of epidermal cell proliferation: detection with an anti-ganglioside GM3 antibody, J. Invest, Dermatol 92: 240-246, 1989. Paller AS, Arnsmeier SL, Alvarez-Franco M., and Bremer EG Ganglioside GM3 inhibits the proliferation of cultured keratinocytes J. Invest. Dermatol 100: 841-845, 1993. Pardoll D. New strategies for active immunotherapy with genetically engineered tumor Curr. Opin. Immunol. 4: 619-23, 1992. Progenies Pharmaceuticals, Inc. Prospectus for sale of 2,000,000 shares of Common Stock subject to completion, dated October 30, 1996. Saleh MN Stapleton, JD Khazaeli MB and LoBuglio , AF Generation of a human anti-idiotypic antibody that mimics the GD2 antigen, J. Immunol. 151: 3390-3398, 1993.

Samonigg H. et al. Immune response to tumor antigens in a patient with colorectal cancer after immunization with anti-idiotype antibody. Clin. Immunol. Immunopathol. 65: 271-277, 1992. Skov L. et al. Lesional psoriatic T cells contain the capacity to induce a T cell activation molecule CDw60 on normal keratinocytes. Am. J. Pathol. 150: 675-683, 1997. Sunday M.E. et al. Differential display RT-PCR for identifying novel gene expression in the lung. Am. J. Physiol. 269: L273-L284, 1995. Yamamoto S. Yamamoto T. Saxton R.E. Hoon D.S.B. and Irie, R.F. Anti-idiotype monoclonal antibody carrying the internal image of ganglioside GM3. J. Natl. Cancer Inst. 82: 1757-1760, 1990. 053,224 E.C DeFreitas et al. Anti-idiotype vaccines 102,663 P.O. Livingston et al. Vaccines for 9-0-acetyl-GD3 141,742 JP. Brown et al. Vaccines of p97 against melanoma 308,614 Hakomori et al. Gangliosides associated with antitumor 330,977 E. Tubaro et al. Looganglioside derivatives 529,922 P.B. Chapman et al. Anti-idiotype vaccine of GD3 612.030 M. Chatterjee et al. Anti-idiotype vaccine of GD2 653,977 M.N. Saleh Vaccine anti-idiotype of GD2 BE 1008391 A. Remake Vaccine of CEA EP-0443518 Y. Nagai et al. Pharmaceutical products of episialo-ganglioside EP-0661061 R.P. Rodriguez et al. N-glycolylated ganglioside vaccines JP-6145069 Nisshin Oil Mills Ltd. Ganglioside angiogenesis inhibitors WO 92/19266 J. Kanton et al. Vaccine vaccine CEA WO 93/10134 H. Magnusson et al. Ganglioside lactam analogs WO 94/16731 Livingston et al. Ganglioside vaccines KLH with QS-21 WO 95/04548 A. Maida et al. Vaccines against prostate cancer WO 96/20277 M. Chatterjee et al. CEA anti-idiotype vaccines WO 96/20219 M. Chatterjee et al. CEA anti-idiotype vaccines WO 96/22373 M. Chatterjee et al. Anti-idiotype vaccines of GD2 WO 97/22694 M. Chatterjee et al. HMFG anti-idiotype vaccines It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (20)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A method for the treatment of psoriasis in an individual, characterized in that the method comprises the administration of a composition comprising an antigen that shares immunological characteristics of an antigen that is aberrantly expressed in human psoriatic tissue, where a specific immune response is promoted. for the aberrantly expressed antigen, in the individual.

2. The method according to claim 1, characterized in that the individual is a human.

3. The method according to claim 1, characterized in that the antigen administered is a ganglioside, and the immune response is an anti-ganglioside immune response.

4. The method according to claim 3, characterized in that the ganglioside being administered is selected from the group consisting of GM2, GM3, GDlb, GD2, 9-O-acetyl-GD2, GD3, GD3-lactone, 9-0-acetyl -GD3 and GT3.

5. The method according to claim 3, characterized in that the ganglioside that is administered is GD2 or 9-0-acetyl-GD2.

6. The method according to claim 1, characterized in that the antigen administered is an anti-idiotype portion for a ganglioside.

7. The method according to claim 6, characterized in that the anti-idiotype portion is 1A7, 4B5 or BEC-2.

8. A method for the preparation of a composition for use in the treatment of psoriasis, characterized in that the method comprises: the production of an anti-idiotype antibody against a monoclonal antibody that binds to an antigenic determinant that is aberrantly expressed in the tissue psoriatic, wherein the anti-idiotype antibody is capable of promoting an immune response in a human against the antigenic determinant.

9. The method according to claim 8, characterized in that the antigenic determinant is identified using the monoclonal antibody against which the anti-idiotype is produced.

10. A method of selecting an immunogenic composition for use in the treatment of psoriasis in humans, characterized in that it comprises the steps of: a) administering, to a plurality of human subjects having psoriasis, an immunogenic composition comprising a form immunogenic of: i) an antigenic determinant that is aberrantly expressed in psoriatic tissue; ii) a monoclonal anti-idiotype antibody for an antigenic determinant that is aberrantly expressed in psoriatic tissue; or iii) an expression vector encoding either i) or ii); and b) the correlation of the progression of psoriasis in the human subjects treated in step a) in relation to that in untreated human subjects having psoriasis, with the effectiveness of the immunogenic composition.

11. A method of selecting an immunogenic composition for use in the treatment of psoriasis in humans, characterized in that it comprises the steps of: a) administering, to a plurality of human subjects having psoriasis, an immunogenic composition comprising a form immunogenic of: i) an antigenic determinant that is aberrantly expressed in psoriatic tissue; ii) a monoclonal anti-idiotype antibody for an antigenic determinant that is aberrantly expressed in psoriatic tissue; or iii) an expression vector encoding either i) or ii); and 51 b) determining the degree of an immunological response against the antigenic determinant in each subject treated in step a); and c) the correlation of the progression of psoriasis in relation to the degree of the immunological response against the antigenic determinant in each subject, with the effectiveness of the immunogenic composition.

12. The method of selection according to claim 10, characterized in that the antigen that is aberrantly expressed in the psoriatic tissue is a ganglioside.

13. The method of selection according to claim 11, characterized in that the antigen that is aberrantly expressed in the psoriatic tissue is a ganglioside.

14. A kit, characterized in that it comprises: a) a composition packaged in a container and comprising an immunogenic form of a component selected from the group consisting of: i) a ganglioside; ii) an anti-idiotype for a ganglioside; and iii) an expression vector that codes for an anti-idiotype for a ganglioside; and b) written instructions for the use of the composition in the treatment of psoriasis.

15. The use of a component selected from the group consisting of: i) a ganglioside; ii) an anti-idiotype for a ganglioside; and iii) an expression vector that codes for an anti-idiotype for a ganglioside; in the manufacture of a medication for the treatment of psoriasis.

16. The use according to claim 15, characterized in that the psoriasis is classified within the group consisting of psoriasis by glutathione, pustular psoriasis, plaque-type psoriasis, and psoriatic arthritis.

17. The use according to claim 15, characterized in that the psoriasis is chronic plaque psoriasis.

18. The use according to claim 15, characterized in that the component is a ganglioside selected from the group consisting of GM2, GM3, GDlb, GD2, 9-0-acetyl-GD2, GD3, GD3-lactone, 9-0-acetyl- GD3 and GT3.

19. The use according to claim 15, characterized in that the component is an anti-idiotype selected from the group consisting of 1A7, 4B5 and BEC-2.

20. A topical formulation, characterized in that it comprises 1A7.