US 12,241,097 B2
Compositions and methods for adoptive cell therapy for cancer
David A. Scheinberg, New York, NY (US); Thomas J. Gardner, New York, NY (US); Derek S. Tan, New York, NY (US); Jonghan Lee, New York, NY (US); and Ivo Lorenz, New York, NY (US)
Assigned to Memorial Sloan Kettering Cancer Center, New York, NY (US)
Appl. No. 16/627,267
Filed by MEMORIAL SLOAN KETTERING CANCER CENTER, New York, NY (US)
PCT Filed Jul. 2, 2018, PCT No. PCT/US2018/040633
§ 371(c)(1), (2) Date Dec. 27, 2019,
PCT Pub. No. WO2019/006465, PCT Pub. Date Jan. 3, 2019.
Claims priority of provisional application 62/527,932, filed on Jun. 30, 2017.
Prior Publication US 2020/0157518 A1, May 21, 2020
Int. Cl. C12N 9/48 (2006.01); A61K 9/00 (2006.01); A61K 35/17 (2015.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07D 239/94 (2006.01); C07D 501/16 (2006.01); C07D 519/00 (2006.01); C07K 14/52 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01)
CPC C12N 9/485 (2013.01) [A61K 9/0019 (2013.01); A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/464412 (2023.05); A61K 39/464453 (2023.05); A61K 39/464454 (2023.05); A61K 39/464489 (2023.05); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 239/94 (2013.01); C07D 501/16 (2013.01); C07D 519/00 (2013.01); C07K 14/52 (2013.01); C07K 16/2803 (2013.01); C12N 5/0636 (2013.01); C12Y 304/17011 (2013.01); A61K 38/00 (2013.01); A61K 2239/48 (2023.05); A61K 2239/49 (2023.05); A61K 2239/50 (2023.05); A61K 2239/55 (2023.05); A61K 2239/59 (2023.05); C07K 2317/24 (2013.01); C07K 2317/622 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/35 (2013.01)] 16 Claims
 
1. An engineered immune cell comprising:
(a) a nucleic acid encoding a first prodrug converting enzyme, wherein the first prodrug converting enzyme is configured to be expressed in the cytoplasm of the immune cell and is selected from among a carboxypeptidase, a β-lactamase, a glucosidase, a nitroreductase, and carboxypeptidase A;
(b) a chimeric antigen receptor comprising a first transmembrane domain, wherein the chimeric antigen receptor is expressed on the surface of the immune cell and binds to a tumor antigen on solid tumors, and/or a nucleic acid encoding the chimeric antigen receptor; and
(c) a nucleic acid encoding a second prodrug converting enzyme, wherein the second prodrug converting enzyme
(i) is configured to be secreted or
(ii) is expressed on the surface of the immune cell and is
(A) attached to the surface of the cell by a GPI anchor; or
(B) fused to a second transmembrane domain; and
wherein the first transmembrane domain of the chimeric antigen receptor is separate from the second transmembrane domain of the second prodrug converting enzyme, and
wherein the engineered immune cell treats solid tumors that are resistant to CAR T cell therapy.