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US 12,662,705 B2Granted
Interferon pathway genes regulate and predict efficacy of immunotherapy
AssigneeThe Trustees of the University of Pennsylvania
InventorAndy J. Minn
Life of this patent
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Abstract
The present invention includes methods for treating cancer and selecting a patient for immunotherapy administration.
Claims14
A method for treating cancer in a subject in need thereof, the method comprising:
- measuring expression level of an interferon stimulating genes resistance signature (ISG.RS) metagene in a tumor from the subject and/or in a cancer cell from the subject;
- measuring expression level of an interferon gene signature (IFNG.GS) metagene in a tumor from the subject and/or in an intratumoral immune cell from the subject;
- and
- administering an immunotherapy comprising an immune checkpoint blockade (ICB) to the subject when the measured expression level of the IFNG.GS metagene is greater than the measured expression level of the ISG.RS metagene, or
- administering an alternative cancer treatment to the subject when the measured expression level of the ISG.RS metagene is greater than the measured expression level of the IFNG.GS metagene, wherein the subject is not administered the immunotherapy,
- thereby treating the cancer in the subject;
- wherein:
- the cancer is melanoma;
- the ISG.RS metagene comprises IFI27, IRF7, USP18, BST2, CXCL10, DDX60, HERC6, HLA-B, HLA-G, IFI35, IFI44, IFI44L, IFIT1, IFIT3, ISG15, LGALS3BP, LY6E, MX1, MX2, OAS3, OASL, PLSCR1, STAT1, TRIM14, HSD17B1, OAS1, CA2, CCNA1, CXCL1, GALC, IFI6, IFITM1, LAMP3, MCL1, ROBO1, SLC6A15, THBS1, and TIMP3;
- and
- the IFNG.GS metagene comprises TNFSF10, IRF9, EPSTI1, PARP12, TRIM25, CASP7, UPP1, B2M, IRF4, SRI, NFKBIA, OAS2, RSAD2, XAF1, SP110, IFITM3, GBP4, IRF8, IFIH1, UBE2L6, ADAR, STAT2, CXCL9, IL10RA, PLA2G4A, TRIM21, PTGS2, DDX58, IL15, NLRC5, NMI, IDO1, PSMB10, CXCL11, SAMD9L, RTP4, PTPN2, TNFAIP2, IFITM2, SOCS1, CASP1, ICAM1, WARS, PSME1, ISG20, FCGR1A, SOCS3, HLA-DMA, TNFAIP6, TRIM26, VCAM1, CD274, CIITA, NAMPT, GPR18, FPR1, PRIC285, PSME2, SERPING1, CCL5, RNF31, SOD2, PSMA3, RNF213, PELI1, CFB, CD86, HLA-DQA1, GCH1, PNP, CCL7, PTPN6, SPPL2A, IL4R, DHX58, CASP8, IFI30, CCL2, FGL2, SECTM1, IL15RA, CD40, HLA-DRB1, GBP6, LCP2, MT2A, RIPK1, PSMB2, TDRD7, HIF1A, PFKP, ZBP1, PDE4B, IL7, BPGM, FTSJD2, AUTS2, RIPK2, MYD88, PSMA2, NOD1, TAPBP, SLC25A28, PTPN1, SSPN, NUP93, MTHFD2, CDKN1A, NFKB1, BATF2, LATS2, IRF5, SLAMF7, ISOC1, P2RY14, STAT3, NCOA3, GZMA, IFNAR2, CD74, RAPGEF6, CASP4, OGFR, ARL4A, LYSMD2, CSF2RB, C1R, METTL7B, ST8SIA4, CD38, PSMB9, BANK1, TOR1B, ITGB7, RBCK1, FAS, LAP3, SAMHD1, CMPK2, MVP, TXNIP, ST3GAL5, PARP14, CASP3, IFIT2, CD69, CMKLR1, TAP1, EIF2AK2, PIM1, XCL1, IL2RB, IRF1, BTG1, CFH, VAMP5, IL18BP, IRF2, ZNFX1, PSMB8, ARID5B, MARCH1, TNFAIP3, APOL6, STAT4, JAK2, PML, TRAFD1, SELP, KLRK1, CIS, EIF4E3, HLA-A, PNPT1, VAMP8, and IL6.
8 more elements
A method for treating cancer in a subject in need thereof, the method comprising:
- measuring expression level of an interferon stimulating genes resistance signature (ISG.RS) metagene in a tumor from the subject and/or in a cancer cell from the subject;
- measuring expression level of an interferon gene signature (IFNG.GS) metagene in a tumor from the subject and/or in an intratumoral immune cell from the subject;
- calculating a ratio of the expression level of the IFNG.GS metagene over the expression level of the ISG.RS metagene;
- and
- administering an immunotherapy comprising an immune checkpoint blockade (ICB) to the subject when the ratio is increased in comparison to that of a reference sample;
- or
- administering an alternative cancer treatment to the subject when the ratio is not increased in comparison to that of a reference sample, wherein the subject is not administered the immunotherapy,
- thereby treating the cancer in the subject;
- wherein:
- the cancer is melanoma;
- the ISG.RS metagene comprises IFI27, IRF7, USP18, BST2, CXCL10, DDX60, HERC6, HLA-B, HLA-G, IFI35, IFI44, IFI44L, IFIT1, IFIT3, ISG15, LGALS3BP, LY6E, MX1, MX2, OAS3, OASL, PLSCR1, STAT1, TRIM14, HSD17B1, OAS1, CA2, CCNA1, CXCL1, GALC, IFI6, IFITM1, LAMP3, MCL1, ROBO1, SLC6A15, THBS1, and TIMP3;
- and
- the IFNG.GS metagene comprises TNFSF10, IRF9, EPSTI1, PARP12, TRIM25, CASP7, UPP1, B2M, IRF4, SRI, NFKBIA, OAS2, RSAD2, XAF1, SP110, IFITM3, GBP4, IRF8, IFIH1, UBE2L6, ADAR, STAT2, CXCL9, IL10RA, PLA2G4A, TRIM21, PTGS2, DDX58, IL15, NLRC5, NMI, IDO1, PSMB10, CXCL11, SAMD9L, RTP4, PTPN2, TNFAIP2, IFITM2, SOCS1, CASP1, ICAM1, WARS, PSME1, ISG20, FCGR1A, SOCS3, HLA-DMA, TNFAIP6, TRIM26, VCAM1, CD274, CIITA, NAMPT, GPR18, FPR1, PRIC285, PSME2, SERPING1, CCL5, RNF31, SOD2, PSMA3, RNF213, PELI1, CFB, CD86, HLA-DQA1, GCH1, PNP, CCL7, PTPN6, SPPL2A, IL4R, DHX58, CASP8, IFI30, CCL2, FGL2, SECTM1, IL15RA, CD40, HLA-DRB1, GBP6, LCP2, MT2A, RIPK1, PSMB2, TDRD7, HIF1A, PFKP, ZBP1, PDE4B, IL7, BPGM, FTSJD2, AUTS2, RIPK2, MYD88, PSMA2, NOD1, TAPBP, SLC25A28, PTPN1, SSPN, NUP93, MTHFD2, CDKN1A, NFKB1, BATF2, LATS2, IRF5, SLAMF7, ISOC1, P2RY14, STAT3, NCOA3, GZMA, IFNAR2, CD74, RAPGEF6, CASP4, OGFR, ARL4A, LYSMD2, CSF2RB, C1R, METTL7B, ST8SIA4, CD38, PSMB9, BANK1, TOR1B, ITGB7, RBCK1, FAS, LAP3, SAMHD1, CMPK2, MVP, TXNIP, ST3GAL5, PARP14, CASP3, IFIT2, CD69, CMKLR1, TAP1, EIF2AK2, PIM1, XCL1, IL2RB, IRF1, BTG1, CFH, VAMP5, IL18BP, IRF2, ZNFX1, PSMB8, ARID5B, MARCH1, TNFAIP3, APOL6, STAT4, JAK2, PML, TRAFD1, SELP, KLRK1, CIS, EIF4E3, HLA-A, PNPT1, VAMP8, and IL6.
10 more elements
Dependencies are inferred from the claim text.