US 11,673,964 B2
Use of CD2/5/7 knock-out anti-CD2/5/7 chimeric antigen receptor T cells against T cell lymphomas and leukemias
Marco Ruella, Ardmore, PA (US); Saar Gill, Philadelphia, PA (US); Carl H. June, Merion Station, PA (US); Avery D. Posey, Philadelphia, PA (US); and Daniel J. Powell, Bala Cynwyd, PA (US)
Assigned to The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Appl. No. 17/416,365
Filed by THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, Philadelphia, PA (US)
PCT Filed Dec. 19, 2019, PCT No. PCT/US2019/067613
§ 371(c)(1), (2) Date Jun. 18, 2021,
PCT Pub. No. WO2020/132327, PCT Pub. Date Jun. 25, 2020.
Claims priority of provisional application 62/782,131, filed on Dec. 19, 2018.
Prior Publication US 2022/0073639 A1, Mar. 10, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 35/17 (2015.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); C07K 14/47 (2006.01)
CPC C07K 16/2896 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07K 14/7051 (2013.01); C07K 14/70507 (2013.01); C07K 14/70578 (2013.01); C07K 14/70596 (2013.01); C07K 16/2803 (2013.01); C07K 16/2806 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); C07K 14/4748 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01)] 20 Claims
 
1. A pharmaceutical composition comprising a first population of T-cells comprising a chimeric antigen receptor (CAR) and a mutated endogenous CD5 gene and a second population of T-cells comprising a mutated endogenous CD5 gene, wherein the second population does not comprise the CAR.
 
11. A method of treating cancer in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 1.
 
15. A method of enhancing the efficacy of a T-cell comprising a chimeric antigen receptor for treating cancer in a subject, the method comprising administering to the subject a T-cell comprising a mutated endogenous CD5 gene and the chimeric antigen receptor, wherein the chimeric antigen receptor does not comprise an antigen binding domain that binds to CD5.
 
18. A chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain that binds to CD5, a transmembrane domain, and an intracellular domain, wherein the antigen binding domain comprises a complementarity determining region (CDR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 83-88 and 95-100.