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US 10,894,093 B2Granted
Method of engineering drug-specific hypersensitive t-cells for immunotherapy by gene inactivation
AssigneeCellectis
InventorsJulien Valton, Veronique Zennou, Philippe Duchateau, Laurent Poirot
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Abstract
The present invention relates to therapeutic cells for immunotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering drug-specific hypersensitive T-cell, which can be depleted in vivo by the administration of said specific drug in case of occurrence of a serious adverse even. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer.
Claims21
A method of producing human immune cells having drug hypersensitivity, said method comprising:
- (a) providing human immune cells:
- (b) inducing drug hypersensitivity in said human cell by selectively cleaving a gene selected from GGH, RhoA, CDK5, CXCR3, NR1 H2, URG4, PARP14, AMPD3, CCDC38, NFU1 and CACNG5 with at least one rare-cutting endonuclease or targeted nickase targeting said gene, wherein the wherein a rare-cutting endonuclease or targeted nickase targets a sequence selected from:
- SEQ ID NO:14, or a sequence having at least 95% identity with SEQ ID NO:15;
- SEQ ID NO:1, or a sequence having at least 95% identity with SEQ ID NO:2;
- SEQ ID NO:3, or a sequence having at least 95% identity with SEQ ID NO:4;
- and SEQ ID NO:6-11, 18-19,16-17, 21-23, 20 and 12-13, or a sequence having at least 95% identity with the SEQ ID NO:6-11, 18-19, 16-17, 21-23, 20 and 12-13;
- (c) selecting for hypersensitivity to said drug of the human cell engineered in step b);
- and (d) expanding the selected engineered immune cells obtained in step c).
5 more elements
Dependencies are inferred from the claim text.