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WO2020169472A3 - Methods of inducing phenotypic changes in macrophages - Google Patents

Methods of inducing phenotypic changes in macrophages Download PDF

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Publication number
WO2020169472A3
WO2020169472A3 PCT/EP2020/053906 EP2020053906W WO2020169472A3 WO 2020169472 A3 WO2020169472 A3 WO 2020169472A3 EP 2020053906 W EP2020053906 W EP 2020053906W WO 2020169472 A3 WO2020169472 A3 WO 2020169472A3
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WIPO (PCT)
Prior art keywords
tumor
tam
macrophages
cholesterol efflux
functions
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Ceased
Application number
PCT/EP2020/053906
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French (fr)
Other versions
WO2020169472A2 (en
Inventor
Toby Lawrence
Pieter GOOSSENS
Juan RODRIGUEZ VITA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aix Marseille Universite
Centre National de la Recherche Scientifique CNRS
Institut National de la Sante et de la Recherche Medicale INSERM
Original Assignee
Aix Marseille Universite
Centre National de la Recherche Scientifique CNRS
Institut National de la Sante et de la Recherche Medicale INSERM
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Publication of WO2020169472A2 publication Critical patent/WO2020169472A2/en
Publication of WO2020169472A3 publication Critical patent/WO2020169472A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P35/00—Antineoplastic agents
    • 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
    • A61K40/17—Monocytes; Macrophages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
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    • 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
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    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A—HUMAN NECESSITIES
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    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0645—Macrophages, e.g. Kuepfer cells in the liver; Monocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
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    • C12N2501/20—Cytokines; Chemokines
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    • C12N2502/30—Coculture with; Conditioned medium produced by tumour cells

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract

Tumor-associated macrophages (TAM) have been shown to have important roles in the malignant progression of various cancers. However, macrophages also possess intrinsic tumoricidal activity and can promote the activity of cytotoxic lymphocytes, but they rapidly adopt an alternative phenotype within tumors, associated with immune-suppression and trophic functions that support tumor growth. The mechanisms that promote TAM polarization in the tumor-microenvironment remain poorly understood, these mechanisms may represent important therapeutic targets to block the tumor-promoting functions of TAM and restore their anti-tumor potential. Here the inventors have characterized TAM in a mouse model of metastatic ovarian cancer. They show that ovarian cancer cells promote membrane-cholesterol efflux and the depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4 mediated reprogramming while inhibiting IFN-induced gene expression. These studies reveal an unexpected role for tumor-induced membrane-cholesterol efflux in driving the IL-4 signaling and the tumor-promoting functions of TAM, while rendering them refractory to pro-inflammatory stimuli. Thus, preventing cholesterol efflux in TAM could represent a novel therapeutic strategy to block pro-tumor functions and restore anti-tumor immunity.
PCT/EP2020/053906 2019-02-18 2020-02-14 Methods of inducing phenotypic changes in macrophages Ceased WO2020169472A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP19305197.6 2019-02-18
EP19305197 2019-02-18

Publications (2)

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WO2020169472A2 WO2020169472A2 (en) 2020-08-27
WO2020169472A3 true WO2020169472A3 (en) 2020-11-05

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CN112877357B (en) * 2020-12-28 2021-12-24 江苏科技大学 Application of Abcg4 gene in constructing animal model with bidirectional change of obesity degree
IT202100006569A1 (en) * 2021-03-18 2022-09-18 Hemera S R L METHOD FOR OBTAINING REGENERATIVE MACROPHAGES EDUCATED FROM TUMOR AND THEIR USE IN REGENERATIVE MEDICINE
CN114767848B (en) * 2022-03-01 2024-05-14 安徽省立医院(中国科学技术大学附属第一医院) Research methods on the mechanism of action of PD-L1 neutralizing antibodies on gout inflammation
CN115029789A (en) * 2022-05-31 2022-09-09 南通大学 Construction of shRNA library of DC-SIGN and its application in primary liver cancer
CN115957304A (en) * 2022-10-18 2023-04-14 山东大学 Application of Tim-4 in regulating and controlling cholesterol synthesis
CN116036285B (en) * 2023-02-07 2024-02-02 河北大学附属医院 Application of substance for inhibiting STAT6 site ubiquitination in regulating macrophage polarization
CN119139348B (en) * 2024-11-20 2025-03-18 昆明医科大学 A cell bionic nanoparticle and its construction method and application

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