WO2022047325A1 - Ciblage de tmg4 pour le traitement du cancer de la prostate - Google Patents

Ciblage de tmg4 pour le traitement du cancer de la prostate Download PDF

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Publication number
WO2022047325A1
WO2022047325A1 PCT/US2021/048273 US2021048273W WO2022047325A1 WO 2022047325 A1 WO2022047325 A1 WO 2022047325A1 US 2021048273 W US2021048273 W US 2021048273W WO 2022047325 A1 WO2022047325 A1 WO 2022047325A1
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WO
WIPO (PCT)
Prior art keywords
tgm4
cells
antibody
subject
prostate cancer
Prior art date
Application number
PCT/US2021/048273
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English (en)
Inventor
Charles G. DRAKE
Zoila Areli LOPEZ-BUJANDA
Original Assignee
The Trustees Of Columbia University In The City Of New York
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Application filed by The Trustees Of Columbia University In The City Of New York filed Critical The Trustees Of Columbia University In The City Of New York
Publication of WO2022047325A1 publication Critical patent/WO2022047325A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4615—Dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
    • A61K39/4622—Antigen presenting cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464454—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/46449—Melanoma antigens
    • A61K39/464492—Glycoprotein 100 [Gp100]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464493—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; Prostatic acid phosphatase [PAP]; Prostate-specific G-protein-coupled receptor [PSGR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/464838—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1025—Acyltransferases (2.3)
    • C12N9/104—Aminoacyltransferases (2.3.2)
    • C12N9/1044—Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y203/00—Acyltransferases (2.3)
    • C12Y203/02—Aminoacyltransferases (2.3.2)
    • C12Y203/02013—Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55522—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/80—Vaccine for a specifically defined cancer
    • A61K2039/884—Vaccine for a specifically defined cancer prostate
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment

Definitions

  • Transglutaminase 4 belongs to the transglutaminase family of proteins. TGM4 is expressed in prostate and has been associated with male subfertility.
  • the agonist is an anti- TGM4 antibody.
  • the antibody is a monoclonal antibody.
  • the antibody is humanized or fully-human.
  • the antibody comprises a fragment of a fully functional anti-TGM4 antibody.
  • the fragment is an ScFv (single chain variable fragment).
  • the TGM4 agonist is further conjugated with a second antitumor reagent.
  • the second anti-tumor reagent is a cytotoxic drug.
  • the top panel shows the immunoprecipitation to detect antibodies against recombinant human TGM4 and PAP in the sera of indicated patients from Fig. 11C.
  • Recombinant proteins were immunoprecipitated under non-denaturing conditions with human antibodies pre and post vaccination and probed with either anti-TGM4 or anti-PAP antibody in Western blot.
  • Fig. 12D shows fold change on recovered recombinant proteins using patient sera post vs pre vaccination. Paired t-tests performed, p values shown.
  • Unsupervised computational analysis was performed separately for unstimulated and stimulated samples.
  • 10,000 cells of postgated live, single CD4+ or CD8+ T cells from each of the 10 healthy donors were randomly selected using the DownSampleV3 plugin in FlowJo.
  • unsupervised clustering was performed on the expression values of the activation and functional markers separately using the FlowSOM algorithm, which uses a self-organizing map followed by hierarchical consensus metaclustering to detect cell populations. Default parameters and a predetermined number of 10 clusters were used. The median levels of the activation and functional markers across all cells per cluster were visualized in separate heatmaps.
  • Fig. 12A shows the PhlP-Seq profiling of a cohort of patients with prostate adenocarcinoma treated with ADT alone or GV AX followed by ADT in a neo-adjuvant trial (NCT01696877).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Transplantation (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne une méthode de traitement du cancer de la prostate par ciblage de la transglutaminase 4 (TGM4) soit seul soit en combinaison avec d'autres thérapies telles que : l'ablation des androgènes, la chimiothérapie, la radiothérapie, les agents à petites molécules ou l'immunothérapie.
PCT/US2021/048273 2020-08-31 2021-08-30 Ciblage de tmg4 pour le traitement du cancer de la prostate WO2022047325A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063072854P 2020-08-31 2020-08-31
US63/072,854 2020-08-31

Publications (1)

Publication Number Publication Date
WO2022047325A1 true WO2022047325A1 (fr) 2022-03-03

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160213754A1 (en) * 2013-09-20 2016-07-28 Nils LANDEGREN Transglutaminase 4 as a prostate specific autoantigen and the methods of use thereof
US20160279214A1 (en) * 2015-03-27 2016-09-29 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against various tumors
US20160304883A1 (en) * 2013-12-30 2016-10-20 Curevac Ag Artificial nucleic acid molecules
US20190324030A1 (en) * 2016-06-27 2019-10-24 Juno Therapeutics, Inc. Mhc-e restricted epitopes, binding molecules and related methods and uses
WO2020205778A1 (fr) * 2019-03-30 2020-10-08 Biontech Us Inc. Compositions et procédés de préparation de compositions de lymphocytes t et leurs utilisations

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160213754A1 (en) * 2013-09-20 2016-07-28 Nils LANDEGREN Transglutaminase 4 as a prostate specific autoantigen and the methods of use thereof
US20160304883A1 (en) * 2013-12-30 2016-10-20 Curevac Ag Artificial nucleic acid molecules
US20160279214A1 (en) * 2015-03-27 2016-09-29 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against various tumors
US20190324030A1 (en) * 2016-06-27 2019-10-24 Juno Therapeutics, Inc. Mhc-e restricted epitopes, binding molecules and related methods and uses
WO2020205778A1 (fr) * 2019-03-30 2020-10-08 Biontech Us Inc. Compositions et procédés de préparation de compositions de lymphocytes t et leurs utilisations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CAO ZHI, WANG YANG, LIU ZHI-YONG, ZHANG ZHEN-SHENG, REN SHAN-CHENG, YU YONG-WEI, QIAO MENG, ZHAI BEI-BEI, SUN YING-HAO: "Overexpression of transglutaminase 4 and prostate cancer progression: a potential predictor of less favourable outcomes", ASIAN JOURNAL OF ANDROLOGY, NATURE PUBLISHING GROUP, US, vol. 15, no. 6, 1 November 2013 (2013-11-01), US , pages 742 - 746, XP055912033, ISSN: 1008-682X, DOI: 10.1038/aja.2013.79 *

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WO2022047325A1 (fr) Ciblage de tmg4 pour le traitement du cancer de la prostate

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