title: Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy.
abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody yields durable responses in a subset of cancer patients and has been approved by the FDA as a standard therapy for late-stage melanoma. We recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong support for the development of combinatorial therapies incorporating anti-CTLA-4 and ICOS engagement.
authors.affiliation: Department of Immunology and 2 Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Fan
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Quezada
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Sepulveda
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D017951:Antigen Presentation / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007156:Immunologic Memory / Q000187:drug effects; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism*; D008024:Ligands; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands