US 11,913,075 B2
Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer
Aviv Regev, Cambridge, MA (US); Orit Rozenblatt-Rosen, Cambridge, MA (US); Benjamin Izar, Boston, MA (US); Livnat Jerby, Cambridge, MA (US); and Asaf Rotem, Boston, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Appl. No. 16/499,908
Filed by The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
PCT Filed Mar. 30, 2018, PCT No. PCT/US2018/025507
§ 371(c)(1), (2) Date Oct. 1, 2019,
PCT Pub. No. WO2018/183921, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/630,158, filed on Feb. 13, 2018.
Claims priority of provisional application 62/595,327, filed on Dec. 6, 2017.
Claims priority of provisional application 62/588,025, filed on Nov. 17, 2017.
Claims priority of provisional application 62/573,117, filed on Oct. 16, 2017.
Claims priority of provisional application 62/567,153, filed on Oct. 2, 2017.
Claims priority of provisional application 62/519,784, filed on Jun. 14, 2017.
Claims priority of provisional application 62/480,407, filed on Apr. 1, 2017.
Prior Publication US 2020/0157633 A1, May 21, 2020
Int. Cl. C12Q 1/68 (2018.01); C12Q 1/6886 (2018.01)
CPC C12Q 1/6886 (2013.01) [C12Q 2600/106 (2013.01); C12Q 2600/158 (2013.01)] 10 Claims
 
1. A method of treating a cancer in a subject comprising detecting whether an immune checkpoint inhibitor resistance (ICR) gene signature is expressed in malignant cells from a solid tumor sample obtained from the subject and administering a treatment,
wherein the ICR gene signature comprises upregulation of C1QBP, CCT2, CCT6A, DCAF13, EIF4A1, ILF2, MAGEA4, NONO, PA2G4, PGAM1, PPA1, PPIA, RPL18A, RPL26, RPL31, RPS11, RPS15, RPS21, RPS5, RUVBL2, SAE1, SNRPE, UBA52, UQCRH and VDAC2; and, optionally, downregulation of AEBP1, AHNAK, APOC2, APOD, APOE, B2M, C10orf54, CD63, CTSD, EEA1, EMP1, FBXO32, FYB, GATSL3, HCP5, HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-H, ITGA3, LAMP2, LYRM9, MFGE8, MIA, NPC2, NSG1, PROS1, RDH5, SERPINA1, TAPBP, TIMP2, TNFSF4 and TRIML2, as compared to a reference level,
wherein if an ICR gene signature is detected in malignant cells the treatment comprises administering an agent capable of reducing expression or activity of said signature, wherein the agent comprises a small molecule CDK4/6 inhibitor selected from the group consisting of abemaciclib, palbociclib, and ribociclib, and
wherein if an ICR gene signature is not detected the treatment comprises administering an immunotherapy.