WO2024026707A1 - Systèmes de récepteurs antigéniques chimériques, procédés de préparation et utilisations de ceux-ci - Google Patents
Systèmes de récepteurs antigéniques chimériques, procédés de préparation et utilisations de ceux-ci Download PDFInfo
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- WO2024026707A1 WO2024026707A1 PCT/CN2022/109857 CN2022109857W WO2024026707A1 WO 2024026707 A1 WO2024026707 A1 WO 2024026707A1 CN 2022109857 W CN2022109857 W CN 2022109857W WO 2024026707 A1 WO2024026707 A1 WO 2024026707A1
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- exogenous antigen
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- A61K39/461—Cellular immunotherapy characterised by the cell type used
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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Abstract
La présente divulgation concerne un système de CAR intelligent, où un antigène exogène est marqué sur des cellules tumorales, les cellules tumorales marquées avec l'antigène exogène peuvent être reconnues par des cellules immunitaires ingéniérisées qui expriment un récepteur chimérique comprenant un domaine de liaison qui se lie à l'antigène exogène, et la tumeur peut être éliminée au moins en partie. La présente divulgation concerne également des procédés de préparation, des procédés de traitement et des utilisations associées au système de CAR intelligent.
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PCT/CN2022/109857 WO2024026707A1 (fr) | 2022-08-03 | 2022-08-03 | Systèmes de récepteurs antigéniques chimériques, procédés de préparation et utilisations de ceux-ci |
PCT/CN2023/110768 WO2024027764A2 (fr) | 2022-08-03 | 2023-08-02 | Systèmes de récepteurs antigéniques chimériques, procédés de préparation et utilisations de ceux-ci |
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PCT/CN2022/109857 WO2024026707A1 (fr) | 2022-08-03 | 2022-08-03 | Systèmes de récepteurs antigéniques chimériques, procédés de préparation et utilisations de ceux-ci |
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PCT/CN2023/110768 WO2024027764A2 (fr) | 2022-08-03 | 2023-08-02 | Systèmes de récepteurs antigéniques chimériques, procédés de préparation et utilisations de ceux-ci |
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AU2020206359A1 (en) * | 2019-01-10 | 2021-07-29 | Innovative Cellular Therapeutics Holdings, Ltd. | Modified cell expansion and uses thereof |
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Non-Patent Citations (23)
Title |
---|
BRADSHAW, W.J. ET AL.: "Molecular features of the sortase enzyme family", FEBS J, vol. 282, 2015, pages 2097 - 2114 |
CHAMPIAT STSELIKAS LFARHANE SRAOULT TTEXIER MLANOY E ET AL.: "Intratumoral Immunotherapy: From Trial Design to Clinical Practice", CLIN CANCER RES., vol. 27, no. 3, 2021, pages 665 - 79 |
CHEN, I.DORR, B.M.LIU, D.R.: "A general strategy for the evolution of bond-forming enzymes using yeast display", PROC NATL ACAD SCI USA, vol. 108, 2011, pages 11399 - 11404, XP055299966, DOI: 10.1073/pnas.1101046108 |
CHEN, L. ET AL.: "Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency", SCI REP, vol. 6, 2016, pages 31899 |
DAVID T. RODGERS ET AL: "Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 113, no. 4, 26 January 2016 (2016-01-26), pages E459 - E468, XP055260066, ISSN: 0027-8424, DOI: 10.1073/pnas.1524155113 * |
GE YCHEN LLIU SZHAO JZHANG HCHEN PR: "Enzyme-Mediated Intercellular Proximity Labeling for Detecting Cell-Cell Interactions", J AM CHEM SOC., vol. 141, no. 5, 2019, pages 1833 - 7, XP055726676, DOI: 10.1021/jacs.8b10286 |
GE, Y. ET AL.: "Enzyme-Mediated Intercellular Proximity Labeling for Detecting Cell-Cell Interactions", JAM CHEM SOC, vol. 141, 2019, pages 1833 - 1837, XP055726676, DOI: 10.1021/jacs.8b10286 |
GLASGOW, J.E.SALIT, M.L.COCHRAN, J.R: "In Vivo Site-Specific Protein Tagging with Diverse Amines Using an Engineered Sortase Variant", JAM CHEM SOC, vol. 138, 2016, pages 7496 - 7499, XP055576669, DOI: 10.1021/jacs.6b03836 |
MARABELLE ATSELIKAS LDE BAERE THOUOT R: "Intratumoral immunotherapy: using the tumor as the remedy", ANN ONCOL., vol. 28, 2017, pages xii33 - xii43, XP055724506, DOI: 10.1093/annonc/mdx683 |
MAROFI FMOTAVALLI RSAFONOV VATHANGAVELU LYUMASHEV AVALEXANDER M ET AL.: "CAR T cells in solid tumors: challenges and opportunities", STEM CELL RES THER., vol. 12, no. 1, 2021, pages 81 |
MARTINEZ MMOON EK: "CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment", FRONT IMMUNOL, vol. 10, 2019, pages 128, XP055727858, DOI: 10.3389/fimmu.2019.00128 |
MELERO ICASTANON EALVAREZ MCHAMPIAT SMARABELLE A: "Intratumoural administration and tumour tissue targeting of cancer immunotherapies", NAT REV CLIN ONCOL., vol. 18, no. 9, 2021, pages 558 - 76, XP037541763, DOI: 10.1038/s41571-021-00507-y |
PARK KYOUNGSOOK ET AL: "Anchoring foreign substances on live cell surfaces using Sortase A specific binding peptide", CHEMICAL COMMUNICATIONS, vol. 49, no. 83, 1 January 2013 (2013-01-01), UK, pages 9585 - 9587, XP093015205, ISSN: 1359-7345, Retrieved from the Internet <URL:https://pubs.rsc.org/en/content/articlepdf/2013/cc/c3cc44753g> DOI: 10.1039/c3cc44753g * |
PASQUAL GIULIA ET AL: "Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic labelling", NATURE, vol. 553, no. 7689, 1 January 2018 (2018-01-01), London, pages 496 - 500, XP093016044, ISSN: 0028-0836, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853129/pdf/nihms947051.pdf> DOI: 10.1038/nature25442 * |
PHILIP MSCHIETINGER A: "CD8(+) T cell differentiation and dysfunction in cancer", NAT REV IMMUNOL, 2021 |
PISHESHA NINGRAM JRPLOEGH HLSORTASE A: "A Model for Transpeptidation and Its Biological Applications", ANNU REV CELL DEV BIOL., vol. 34, 2018, pages 163 - 88 |
PODRACKY, C.J. ET AL.: "Laboratory evolution of a sortase enzyme that modifies amyloid-beta protein", NAT CHEM BIOL, vol. 17, 2021, pages 317 - 325, XP037378486, DOI: 10.1038/s41589-020-00706-1 |
POPE M.E.SOSTE M.V.EYFORD B.A.ANDERSON N.L.PEARSON T.W., J. IMMUNOL. METHODS., vol. 341, no. 1-2, 2009, pages 86 - 96 |
QIN WU ET AL: "Hepta-Mutant Staphylococcus aureus Sortase A (SrtA 7m ) as a Tool for in Vivo Protein Labeling in Caenorhabditis elegans", ACS CHEMICAL BIOLOGY, vol. 12, no. 3, 18 January 2017 (2017-01-18), pages 664 - 673, XP055515863, ISSN: 1554-8929, DOI: 10.1021/acschembio.6b00998 * |
RODGERS DTMAZAGOVA MHAMPTON ENCAO YRAMADOSS NSHARDY IR ET AL.: "Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies", PROC NATL ACAD SCI U S A., vol. 113, no. 4, 2016, pages E459 - 68, XP055260066, DOI: 10.1073/pnas.1524155113 |
SHARMA PHU-LIESKOVAN SWARGO JARIBAS A: "Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy", CELL, vol. 168, no. 4, 2017, pages 707 - 23, XP029935389, DOI: 10.1016/j.cell.2017.01.017 |
YUN GE ET AL: "Enzyme-Mediated Intercellular Proximity Labeling for Detecting Cell?Cell Interactions", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 141, no. 5, 24 January 2019 (2019-01-24), pages 1833 - 1837, XP055726676, ISSN: 0002-7863, DOI: 10.1021/jacs.8b10286 * |
ZONG YBICE TWTON-THAT HSCHNEEWIND ONARAYANA SV: "Crystal structures of Staphylococcus aureus sortase A and its substrate complex", J BIOL CHEM., vol. 279, no. 30, 2004, pages 31383 - 9 |
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