Title:
IN VIVO AND IN VITRO EDITING PREPARATION METHOD FOR CAR-MΦ TARGETING TUMOR STEM CELLS, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2024/027223
Kind Code:
A1
Abstract:
The present invention provides an in vivo and in vitro editing preparation method for CAR-MΦ targeting tumor stem cells, and a use thereof. The invention provides a chimeric antigen receptor-macrophage (CAR-MΦ) and a nano-carrier based on self-assembled nano-micelles, which can be applied to immunotherapy of brain glioma. According to the present invention, (PA)2 peptide nano-micelles loaded with CD133-CAR plasmids are constructed, and a citric acid anhydride-modified glucan, which is a group targeting macrophage specific target CD206, is adopted for modification. The carrier is used to realize CAR editing of macrophage in vivo and in vitro, so as to facilitate the re-education of tumor-related macrophage from an M2 phenotype to an M1 phenotype. At the same time, the surface markers of tumor stem cells are targeted to accurately target the tumor stem cells, phagocytize tumor cells, activate tumor immunity, remodel the tumor inhibition microenvironment and specifically kill brain glioma stem cells, thereby efficiently treating brain glioma.
Inventors:
JIANG XINYI (CN)
CHEN CHEN (CN)
JING WEIQIANG (CN)
CHEN CHEN (CN)
JING WEIQIANG (CN)
Application Number:
PCT/CN2023/090490
Publication Date:
February 08, 2024
Filing Date:
April 25, 2023
Export Citation:
Assignee:
UNIV SHANDONG (CN)
International Classes:
A61K9/107; C07K19/00; A61K39/00; A61K47/42; A61K47/54; A61K47/61; A61K47/69; A61P35/00; C12N5/10
Foreign References:
| CN115925975A | 2023-04-07 | |||
| CN107793482A | 2018-03-13 | |||
| CN110526970A | 2019-12-03 | |||
| CN113214408A | 2021-08-06 | |||
| CN105378084A | 2016-03-02 | |||
| CN113234162A | 2021-08-10 | |||
| CN103068850A | 2013-04-24 |
Other References:
CHEN, CHEN ET AL.: "Intracavity Generation of Glioma Stem Cell–Specific CAR Macrophages Primes Locoregional Immunity for Postoperative Glioblastoma Therapy", SCIENCE TRANSLATIONAL MEDICINE, vol. 14, 3 August 2022 (2022-08-03), XP093119817, DOI: 10.1126/scitranslmed.abn1128
KAI HAN; WEI‐YUN ZHANG; JIN ZHANG; QI LEI; SHI‐BO WANG; JIA‐WEI LIU; XIAN‐ZHENG ZHANG; HE‐YOU HAN: "Acidity‐Triggered Tumor‐Targeted Chimeric Peptide for Enhanced Intra‐Nuclear Photodynamic Therapy", ADVANCED FUNCTIONAL MATERIALS, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 26, no. 24, 15 March 2016 (2016-03-15), DE , pages 4351 - 4361, XP072411213, ISSN: 1616-301X, DOI: 10.1002/adfm.201600170
KLICHINSKY, MICHAEL ET AL.: "Human Chimeric Antigen Receptor Macrophages for Cancer Immunotherapy", NATURE BIOTECHNOLOGY, vol. 38, no. 8, 31 August 2020 (2020-08-31), XP055926928, DOI: 10.1038/s41587-020-0462-y
KAI HAN; WEI‐YUN ZHANG; JIN ZHANG; QI LEI; SHI‐BO WANG; JIA‐WEI LIU; XIAN‐ZHENG ZHANG; HE‐YOU HAN: "Acidity‐Triggered Tumor‐Targeted Chimeric Peptide for Enhanced Intra‐Nuclear Photodynamic Therapy", ADVANCED FUNCTIONAL MATERIALS, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 26, no. 24, 15 March 2016 (2016-03-15), DE , pages 4351 - 4361, XP072411213, ISSN: 1616-301X, DOI: 10.1002/adfm.201600170
KLICHINSKY, MICHAEL ET AL.: "Human Chimeric Antigen Receptor Macrophages for Cancer Immunotherapy", NATURE BIOTECHNOLOGY, vol. 38, no. 8, 31 August 2020 (2020-08-31), XP055926928, DOI: 10.1038/s41587-020-0462-y
Attorney, Agent or Firm:
JINAN SHENGDA INTELLECTUAL PROPERTY AGENCY CO., LTD. (CN)
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