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WO2021167418A2 - Nouvelle olfm4 de protéine antigénique associée à une tumeur et utilisations associées - Google Patents

Nouvelle olfm4 de protéine antigénique associée à une tumeur et utilisations associées Download PDF

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Publication number
WO2021167418A2
WO2021167418A2 PCT/KR2021/002157 KR2021002157W WO2021167418A2 WO 2021167418 A2 WO2021167418 A2 WO 2021167418A2 KR 2021002157 W KR2021002157 W KR 2021002157W WO 2021167418 A2 WO2021167418 A2 WO 2021167418A2
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WIPO (PCT)
Prior art keywords
seq
antigen
cancer
olfm4
cells
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Ceased
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PCT/KR2021/002157
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English (en)
Korean (ko)
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WO2021167418A3 (fr
Inventor
성승용
박현미
백범서
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SNU R&DB Foundation
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Seoul National University R&DB Foundation
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/34—Antigenic peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/19—Dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/24—Antigen-presenting cells [APC]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • 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
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • An object of the present invention is a novel tumor-associated antigen protein for use in cancer immunotherapy, an antigen-presenting cell comprising the tumor-associated antigen protein, or cytotoxicity induced from the antigen-presenting cell To provide T lymphocytes.
  • the present invention provides an OLFM4 (olfactomedin 4) tumor-associated antigen protein comprising the amino acid sequence of SEQ ID NO: 1.
  • RRIPNRRPRR HRSV, SEQ ID NO: 15
  • DAATATRGRSAASRPTERPRAPARSASRPRRPVE VP22, SEQ ID NO: 16
  • YARVRRRGPRR Hph-1, SEQ ID NO: 17
  • RRRRRRRRRRR R11, SEQ ID NO: 18
  • RRRRRRRRR R9, SEQ ID NO: 19
  • AANLLPNLLAAP MTM, SEQ ID NO: 20
  • AAVALLPAVLLALLAP Signal sequence based peptide, SEQ ID NO: 21
  • ANTP SEQ ID NO: 2
  • the ANTP consisting of the amino acid sequence of SEQ ID NO: 2 may be further conjugated.
  • the cell penetrating peptide is further conjugated to the OLFM4 protein, delivery of the OLFM4 protein to the cytoplasm of the antigen-presenting cell can be improved. Therefore, cell-penetrating peptides capable of enhancing protein delivery into the cytoplasm of cells can be conjugated to OLFM4.
  • the antigen-presenting cells may be used by themselves or in combination with other drugs including cytotoxic T lymphocytes.
  • OLFM4 (olfactomedin 4) or ANTP (antennapedia peptide)-conjugated OLFM4 recombinant protein preparation
  • the membrane was reacted with an HRP-conjugated goat anti-mouse IgG antibody (SantaCruz, California, USA) as a secondary antibody for 1 h at room temperature and washed, followed by ECL solution (Amersham, Piscataway, NJ) and LAS-4000 (FUJIFILM). , FL, Miami Beach) was used to detect an immunoreactive band (FIG. 2a).
  • the purified protein was separated by electrophoresis on a 10% SDS-PAGE gel, and then a band was detected by performing Coomassie blue staining ( FIG. 2b ).
  • FIG. 3a co-stimulatory molecules CD40, CD86, CD80, and I-Ab as maturation markers of dendritic cells were used in the same manner as described above. It was confirmed by performing FACS analysis, and in this case, an anti-CD40 antibody, an anti-CD86 antibody, an anti-CD80 antibody, and an anti-I-Ab antibody were used as primary antibodies ( FIG. 3C ).
  • the lymphocytes harvested above as effector cells were activated in vitro with 10 ⁇ g/ml of hOLFM4 protein for 3 days.
  • the activated effector cells and the mixed target cells were mixed in a ratio of 1:1, 20:1, or 40:1. After 16 hours, target cells were analyzed by FACS LSR Fortesa (BD Biosciences, Mountain View, CA).

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

Abstract

La présente invention concerne une nouvelle olfactomédine 4 (OLFM4) de protéine antigénique associée à une tumeur et des utilisations associées. Spécifiquement, il a été confirmé que des cellules dendritiques chargées d'une OLFM4 ou d'une protéine recombinante OLFM4 conjuguée à un peptide antennapedia (ANTP) induit une réponse immunitaire cytotoxique spécifique à une tumeur et ainsi, l'utilisation de l'OLFM4 en tant que protéine antigénique associée à une tumeur, des cellules présentatrices d'antigène chargées avec la protéine antigénique associée à une tumeur ou des lymphocytes T cytotoxiques dérivés des cellules présentatrices d'antigène peuvent être avantageusement utilisées pour l'immunothérapie anticancéreuse.
PCT/KR2021/002157 2020-02-19 2021-02-19 Nouvelle olfm4 de protéine antigénique associée à une tumeur et utilisations associées Ceased WO2021167418A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2020-0020231 2020-02-19
KR1020200020231A KR102397922B1 (ko) 2020-02-19 2020-02-19 신규한 종양-관련 항원 단백질 olfm4 및 이의 용도

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WO2021167418A2 true WO2021167418A2 (fr) 2021-08-26
WO2021167418A3 WO2021167418A3 (fr) 2021-10-14

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KR20250102259A (ko) 2023-12-27 2025-07-07 중원대학교 산학협력단 IL5Ra 유래 신규 면역원성 펩타이드 및 이의 용도

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GB9814527D0 (en) * 1998-07-03 1998-09-02 Cyclacel Ltd Delivery system
US6559279B1 (en) * 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
WO2002064057A2 (fr) * 2001-02-15 2002-08-22 Baylor College Of Medicine Utilisation de peptides de penetration de cellules pour provoquer une immunite antitumorale
KR100585456B1 (ko) 2003-09-30 2006-06-07 국립암센터 동종 종양-관련 항원이 탑재된 수지상세포, 이의 제조방법및 이를 유효성분으로 하는 암 치료용 백신 조성물
KR100982186B1 (ko) 2010-01-21 2010-09-14 전남대학교산학협력단 신규한 종양 항원 단백질 ａｇｒ２ 및 이의 종양 항원성 펩티드
GB201004551D0 (en) * 2010-03-19 2010-05-05 Immatics Biotechnologies Gmbh NOvel immunotherapy against several tumors including gastrointestinal and gastric cancer
KR101224466B1 (ko) 2010-05-20 2013-01-22 가톨릭대학교 산학협력단 토포아이소머라아제 2 알파 유래의 종양항원 단백질, 유전자, 또는 펩타이드
US9381210B2 (en) 2013-04-15 2016-07-05 Wisconsin Alumni Research Foundation Induced pluripotent stem cell model of chronic myeloid leukemia revealed olfactomedin 4 as a novel therapeutic target in leukemia stem cells
RS67172B1 (sr) * 2016-03-31 2025-09-30 Biontech Us Inc Neoantigeni i postupci za njihovu upotrebu

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KR102397922B1 (ko) 2022-05-13
WO2021167418A3 (fr) 2021-10-14
KR20210105587A (ko) 2021-08-27

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