Method to generate improving car-t cells

The present invention relates to the adoptive therapy using notably CAR-T cells. Here
the inventors used a lentiviral vector approach to silence RINF expression in a shRNA dependent manner and evaluate the consequences of RINF silencing on human CAR-T cells proliferation ex vivo and their functionality and capacity to eradicate tumor cells in vivo. More, the proposed methodology to improve CAR-T cells persistence and efficacy by disrupting RINF/CXXC5 is not restricted to patients suffering from hematological or solid cancers (anti-CD19, anti-EGFR, anti-BCMA…) but could be also used to improve the efficacy of ACT in non-cancer diseases by such as lupus (1), cardiac fibrosis (2) or aging related-disorders (3).
Thus, the present invention relates to an immune cell characterized in that it is defective for RINF.

Patent Application number: European Procedure (Patents) (EPA) - 07 Oct. 2022 - 22 306 511.1
Inventors:
PENDINO Frédéric,DONNADIEU Emmanuel,AN Dongjie,FUMAGALLI Mattia
Publications:
Astori A, Matherat G, Munoz I, Gautier EF, Surdez D, Zermati Y, Verdier F, Zaidi S, Feuillet V, Kadi A, Lauret E, Delattre O, Lefèvre C, Fontenay M, Ségal-Bendirdjian E, Dusanter-Fourt I, Bouscary D, Hermine O, Mayeux P, Pendino F. The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cells expansion. Haematologica. 2022 Jan 1;107(1):268-283. doi: 10.3324/haematol.2020.263558. PMID: 33241676; PMCID: PMC8719099.

Reference:

BIO21116-T1

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Rare disease: No
Second indication: No

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