US 11,702,472 B2
Method of reducing mesothelin-expressing tumor burden by administration of T cells comprising mesothelin-targeted chimeric antigen receptors
Prasad S. Adusumilli, New York, NY (US); Michel Sadelain, New York, NY (US); Dimiter S. Dimitrov, Frederick, MD (US); and Yang Feng, Frederick, MD (US)
Assigned to MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US); and THE U.S.A. AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, Bethesda, MD (US)
Filed by MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US); and The U.S.A. as Represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed on Mar. 17, 2020, as Appl. No. 16/821,674.
Application 16/821,674 is a division of application No. 15/368,278, filed on Dec. 2, 2016, granted, now 10,633,441.
Application 15/368,278 is a continuation of application No. PCT/US2015/034552, filed on Jun. 5, 2015.
Claims priority of provisional application 62/008,851, filed on Jun. 6, 2014.
Prior Publication US 2020/0239569 A1, Jul. 30, 2020
Int. Cl. C07K 16/28 (2006.01); C07K 14/725 (2006.01); C07K 16/30 (2006.01); C07K 14/705 (2006.01); C07K 14/47 (2006.01); A61K 39/00 (2006.01); A61K 38/00 (2006.01); A61K 35/00 (2006.01)
CPC C07K 16/28 (2013.01) [C07K 14/4748 (2013.01); C07K 14/705 (2013.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70521 (2013.01); C07K 16/30 (2013.01); A61K 35/00 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); C07K 2317/21 (2013.01); C07K 2317/54 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01)] 31 Claims
 
1. A method of reducing mesothelin-expressing tumor burden in a subject and/or increasing survival of a subject having a mesothelin-expressing neoplasm, comprising administering to the subject in need thereof an effective amount of T cells comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular antigen-binding domain, a transmembrane domain, and an intracellular domain, wherein the extracellular antigen-binding domain specifically binds to human mesothelin comprises: (a) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 12, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 13; and (b) a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:14, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:15, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16.