CN103736081A

CN103736081A - Application of ONTAK in preparing medicine for eliminating latent HIV (Human Immunodeficiency Virus)

Info

Publication number: CN103736081A
Application number: CN201310700595.7A
Authority: CN
Inventors: 李宁; 焦艳梅; 张永宏; 孙丽君; 李威; 陈德喜; 张彤; 吴昊
Original assignee: Beijing Youan Hospital
Current assignee: Beijing Youan Hospital
Priority date: 2013-12-18
Filing date: 2013-12-18
Publication date: 2014-04-23

Abstract

The invention relates to novel use of ONTAK, which means an application of ONTAK in preparing a medicine for eliminating latent HIV (Human Immunodeficiency Virus). Specific immunoreaction of HIV can be increased and latent HIV can be activated to facilitate elimination of the latent HIV virus by applying ONTAK to long-term ART (Antiretroviral Therapy) treatment effective AIDS (Acquired Immune Deficiency Syndrome) patients.

Description

ONTAK removes the application of hiding in HIV virus drugs in preparation

Technical field

The present invention relates to medical purposes, be specifically related to ONTAK and remove and in HIV virus drugs, apply incubation period in preparation.

Background technology

Since HIV (human immunodeficiency virus) virus is found, occurred the medicine of a variety of anti HIV-1 virus, these medicines can be suppressed to HIV virus the level can't detect and can effectively prevent the generation of the complication that AIDS is relevant.Due to the existence of the HIV virus of hiding, although current anti HIV-1 virus medicine can effectively suppress copying of virus, can not remove virus completely, patient HIV cannot drug withdrawal, need to take medicine all the life.The HIV virus of hiding becomes the obstacle of radical cure HIV virus.Research on latent infection cell model shows, the HIV virus of hiding is in resting state, once but have the viral ability of producing after activation.Due to the existence of the HIV virus of hiding, need lifelong antiviral therapy.Lifelong antiviral therapy have a lot of defects as the toxic and side effects of: medicine, cause drug resistance, increase the financial burden of antiviral therapy etc.So, invent very urgent for the medicine of the HIV virus of hiding.

Also attempt both at home and abroad some means and activate and eliminate the medicine of HIV virus of hiding.Early stage application IL-2 activates in conjunction with CD3 antibody the HIV virus of hiding and proves that it is invalid in HIV virus is hidden in removing.Up-to-date research focuses on the small-molecule drug that can activate the HIV virus of hiding.Have the medicine that is used for the treatment of other diseases of two kinds of U.S. FDAs approval, valproic acid (valproic acid) and SAHA(suberoylanilide hydroxamic acid), the HIV cell that confirmation can activating dormant infection on cell model.But clinical experiment shows that it is invalid annihilating aspect the HIV of latent infection.Virus [the Shan L that first stimulates the special ctl response of HIV to be conducive to annihilate before the HIV virus that the research of Shan etc. is found to hide in activation to hide; Deng K; Shroff NS; Durand CM; Rabi SA; Yang HC, et al.Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation.Immunity2012; 36:491-501.].

ONTAK(denileukin denileukin diftitox) be to be produced by Seragen company and EliLilly company, the consistent recommendation license that obtains FDA consultative committee in the U.S. is used for the treatment of adult's recurrent or persistence cutaneous T cell lymphoma.Have and report that researcher is just being devoted to the treatment for other cancer by this medicine, for example ovarian cancer, breast carcinoma, pulmonary carcinoma, there is not yet report but this medicine is used for the treatment of AIDS.

Summary of the invention

The object of this invention is to provide ONTAK in the application of preparing in the medicine of removing the HIV virus of hiding.

For addressing the above problem, the present invention by the following technical solutions:

ONTAK removes the application of hiding in HIV virus drugs in preparation.

Application as above, preferably, described in hide that HIV virus refers at present can not be by the HIV virus of its removing through antiretroviral drugs treatment, be the main cause that current aids patient can not drug withdrawal, hide HIV virus in resting state, once activation still has the viral ability of producing.

Application as above, preferably, the described removing HIV virus drugs of hiding is injection or lyophilized powder.

Beneficial effect of the present invention is as follows: for the HIV virus of hiding, there is no effective measures at present, at present both at home and abroad research thinks to have that to activate medicine or the target spot of hiding HIV virus and increase the special ctl response of HIV be the measure of effectively removing the HIV virus of hiding.Researcher of the present invention is found at permanently effective ART(antiretroviral drugs) after treatment, ONTAK can activate the HIV virus of hiding effectively, increases HIV special ctl response, reduces HIV virus quantity.Therefore, ONTAK is the effective measures of removing the HIV virus of hiding.

Accompanying drawing explanation

Fig. 1 is HIV specific CTL reaction after a group patient P BMCs does not process and processes with ONTAK.

Fig. 2 is HIV specific CTL reaction after b group patient P BMCs does not process and processes with ONTAK.

Fig. 3 is HIV specific CTL reaction after c group patient P BMCs does not process and processes with ONTAK.

Fig. 4 is after a group patient P BMCs does not process and processes with ONTAK, the activation degree of cd4 cell.

Fig. 5 is after b group patient P BMCs does not process and processes with ONTAK, the activation degree of cd4 cell.

Fig. 6 is after c group patient P BMCs does not process and processes with ONTAK, the activation degree of cd4 cell.

Fig. 7 is the level of HIVp24 after a group patient P BMCs does not process and processes with ONTAK.

Fig. 8 is the level of HIVp24 after b group patient P BMCs does not process and processes with ONTAK.

Fig. 9 is the level of HIVp24 after c group patient P BMCs does not process and processes with ONTAK.

The specific embodiment

Embodiment 1ONTAK removes the isolated experiment of the HIV virus of hiding

(1) material

Medicine ONTAK is purchased from Seragen company and EliLilly company;

HIV-1gag p24KC57 is purchased from U.S. company BD (Becton, Dickinson and Company)

Pentamer detectable is purchased from Regius professor (Oxford, United Kingdom)

(2) method

(1) object of study: untreated patient AIDS 10 people (P1-P10) are a group (a), one line anti-AIDS drug treatment patient AIDS 10 people (P11-P20) of 1 year of country are one group (b), and effective patient 10 people of a national line anti-AIDS drug treatment 5 years (P21-P30) are one group (c);

(2) with density－gradient centrifuga－tion method, separate PBMC;

(3) cell culture: add 2x10 in each culture hole ⁶individual cell, PBMC is only used in part cultured cell hole, in addition a part of cell hole except adding same PBMC, also to add the ONTAK(of 0.1 μ g be the ONTAK that adds 0.1 μ g in 500ul cultivating system), cultivate after 72 hours, detect PBMC hole and add special CTL level and the p24 level of activation levels, HIV of the PBMC hole inner cell of ONTAK;

(4) flow cytometer showed: detect the level of the special CTL of HIV with pentamer, detect the activation levels of cell with HLADr and CD38, detect the expression of p24 with HIV-1gag p24KC57.

(3) result

Result, as shown in Fig. 1-Fig. 9, can find out for untreated patient from Fig. 1 result, and after processing with ONTAK, the reaction of HIV specific CTL has very large difference between different patients; From Fig. 2 result, can find out for the treatment patient of 1 year, after processing with ONTAK, the reaction of HIV specific CTL has very large difference between different patients; From Fig. 3 result, can find out for the treatment patient of 5 years, after processing with ONTAK, the reaction of HIV specific CTL all has increase all patients.

From Fig. 4 result, can find out for untreated patient, after processing with ONTAK, the activation of cd4 cell has very large difference between different patients; From Fig. 5 result, can find out for the treatment patient of 1 year, after processing with ONTAK, cd4 cell activation has very large difference between different patients; From Fig. 6 result, can find out for the treatment patient of 5 years, after processing with ONTAK, the activation of cd4 cell all has increase all patients.

From Fig. 7 result, can find out for untreated patient, after processing with ONTAK, the expression of HIV-1p24 has very large difference between different patients; From Fig. 8 result, can find out for the treatment patient of 1 year, after processing with ONTAK, the expression of HIV-1p24 has very large difference between different patients.From Fig. 9 result, can find out for the treatment patient of 5 years, after processing with ONTAK, the expression of HIV-1p24 all has reduction all patients.

The above results can be found out, for 5 years patients' for the treatment of PBMC, uses the rear HIV specific CTL reaction of ONTAK processing all to have increase all patients, and the activation of cd4 cell all has increase all patients, and the expression of HIV-1p24 all has reduction all patients.Illustrate that ONTAK is to long-term ART(antiretroviral drugs) effectively after treatment, the HIV virus of hiding has and activates and elimination effect, is the effective measures of removing the HIV virus of hiding.

Claims

1.ONTAK removes the application of hiding in HIV virus drugs in preparation.

2. application as claimed in claim 1, it is characterized in that, the described HIV of hiding virus refers at present can not be by the HIV virus of its removing through antiretroviral drugs treatment, it is the main cause that current aids patient can not drug withdrawal, hide HIV virus in resting state, once activation still has the viral ability of producing.

3. application as claimed in claim 1, is characterized in that, the described removing HIV virus drugs of hiding is injection or lyophilized powder.