US 12,226,479 B2
Methods and compositions of use of CD8+ tumor infiltrating lymphocyte subtypes and gene signatures thereof
Moshe Sade-Feldman, Boston, MA (US); Keren Yizhak, Cambridge, MA (US); Gad Getz, Boston, MA (US); and Nir Hacohen, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US); and The Broad Institute, Inc., Cambridge, MA (US)
Appl. No. 16/612,485
Filed by THE GENERAL HOSPITAL CORPORATION, Boston, MA (US); and THE BROAD INSTITUTE, INC., Cambridge, MA (US)
PCT Filed May 11, 2018, PCT No. PCT/US2018/032466
§ 371(c)(1), (2) Date Nov. 11, 2019,
PCT Pub. No. WO2018/209324, PCT Pub. Date Nov. 15, 2018.
Claims priority of provisional application 62/574,878, filed on Oct. 20, 2017.
Claims priority of provisional application 62/505,101, filed on May 11, 2017.
Prior Publication US 2020/0147210 A1, May 14, 2020
Int. Cl. A61K 39/395 (2006.01); A61K 38/45 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C12N 5/0783 (2010.01); C12N 15/10 (2006.01); C12Q 1/6886 (2018.01)
CPC A61K 39/3955 (2013.01) [A61K 38/45 (2013.01); A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/46449 (2023.05); A61P 35/00 (2018.01); C12N 5/0636 (2013.01); C12N 15/10 (2013.01); C12Q 1/6886 (2013.01); A61K 2239/57 (2023.05); C12Q 2600/106 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/158 (2013.01); G01N 2800/52 (2013.01)] 5 Claims
 
1. A method of treating melanoma in a checkpoint blockade (CPB) therapy non-responder subject in need thereof comprising administering polyoxometalate-1 (POM-1) and an anti-T-cell immunoglobulin and mucin-domain containing-3 (TIM3) monoclonal antibody to the subject, wherein the subject expresses a checkpoint blockade (CPB) therapy non-responder gene signature in CD8+ tumor infiltrating lymphocytes (TILs), said CPB therapy non-responder gene signature comprising ENTPD1 (CD39) and HAVCR2 (TIM3), wherein the TIM3 monoclonal antibody is an inhibitor of TIM3 activity, and wherein the response is synergistic.