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1. WO2020163569 - LYMPHOCYTES T CHIMÉRIQUES AYANT SUBI UNE ABLATION DE SIRT2

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[ EN ]

WHAT IS CLAIMED IS:

1. A method comprising

(a) collecting lymphocytes from a subject with cancer;

(b) treating the lymphocytes with a Sirt2 inhibitor or genetically modifying the lymphocytes to inhibit or ablate Sirt2 expression.

2. The method of claim 1 , wherein the Sirt2 inhibitor is AGK2, AK-1 , SirReal2, Tenovin-6, Thiomyristoyl, AEM1 , orAEM2.

3. The method of claim 1 , wherein the Sirt2 inhibitor is an siRNA, antisense, or gRNA oligonucleotide.

4. The method of claim 1 , wherein the lymphocytes are genetically modified by inserting a chimeric receptor into the genome of the cell at a location that disrupts expression or activity of an endogenous Sirt2 protein.

5. The method cell of claim 4, wherein the chimeric receptor is a chimeric antigen receptor (CAR) polypeptide.

6. The method of any one of claims 1 to 5, wherein the lymphocytes are tumor infiltrating lymphocytes (TILs).

7. A therapeutic cell produced by the method of any one of claims 1 to 6.

8. A method of providing an anti-cancer immunity in a subject, comprising administering to the subject an effective amount of the therapeutic cells of claim 7, thereby providing an anti-tumor immunity in the subject.

9. The method of claim 8, further comprising administering to the subject a checkpoint inhibitor.

10. The method of claim 9, wherein the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.