US 12,275,802 B2
Compositions and methods for immunotherapy
Victor D. Fedorov, New York, NY (US); and Michel Sadelain, New York, NY (US)
Assigned to MEMORIAL SLOAN KETTERING CANCER CENTER, New York, NY (US)
Filed by MEMORIAL SLOAN KETTERING CANCER CENTER, New York, NY (US)
Filed on Jan. 24, 2022, as Appl. No. 17/583,117.
Application 17/583,117 is a division of application No. 14/851,983, filed on Sep. 11, 2015, granted, now 11,267,901.
Application 14/851,983 is a continuation of application No. PCT/US2014/030671, filed on Mar. 17, 2014.
Claims priority of provisional application 61/802,118, filed on Mar. 15, 2013.
Prior Publication US 2022/0162340 A1, May 26, 2022
Int. Cl. C07K 16/40 (2006.01); A61K 39/00 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 14/73 (2006.01); C12N 5/0783 (2010.01)
CPC C07K 16/40 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4621 (2023.05); A61K 39/4631 (2023.05); A61K 39/4636 (2023.05); A61K 39/46431 (2023.05); A61K 39/46434 (2023.05); A61K 39/464412 (2023.05); A61K 39/464495 (2023.05); C07K 14/7051 (2013.01); C07K 14/70514 (2013.01); C07K 14/70517 (2013.01); C12N 5/0636 (2013.01); C12N 5/0638 (2013.01); A61K 2239/22 (2023.05); A61K 2239/26 (2023.05); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); C07K 2317/622 (2013.01); C07K 2319/30 (2013.01)] 18 Claims
 
1. A method of treating a tumor in a subject, comprising administering to the subject a T cell, wherein the T cell comprises:
a) a chimeric antigen receptor (CAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a first antigen that is expressed at the surface of a cell of the tumor, and an intracellular signaling domain that is capable of activating the immunoresponsive cell and comprises a signaling domain of CD28, and
b) an inhibitory chimeric antigen receptor (iCAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a second antigen that is not expressed on the tumor cell surface, and a signaling domain of an immunoinhibitory receptor selected from the group consisting of CTLA-4, PD-1, LAG-3, 2B4, and BTLA;
wherein binding of the CAR to the first antigen induces cytotoxicity of the T cell, and binding of the iCAR to the second antigen reduces the cytotoxicity of the T cell induced by the CAR.