title: Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy.
abstract: Cytotoxic T-lymphocyte-associated antigen (CTLA-4), also known as CD152, is a co-inhibitory molecule that functions to regulate T-cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including antitumor immunity. Two CTLA-4-blocking antibodies are presently under clinical investigation: ipilimumab and tremelimumab. CTLA-4 blockade has shown promise in treatment of patients with metastatic melanoma, with a recently completed randomized, double-blind phase III trial demonstrating a benefit in overall survival (OS) in the treated population. However, this approach appears to benefit only a subset of patients. Understanding the mechanism(s) of action of CTLA-4 blockade and identifying prognostic immunologic correlates of clinical endpoints to monitor are presently areas of intense investigation. Several immunologic endpoints have been proposed to correlate with clinical activity. This review will focus on the endpoints of immune monitoring described in studies to date and discuss future areas of additional work needed.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Callahan
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood / Q000187:drug effects; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D015415:Biomarkers; D060908:CTLA-4 Antigen; D006684:HLA-DR Antigens / Q000097:blood / Q000187:drug effects; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D000074324:Ipilimumab; D017493:Leukocyte Common Antigens / Q000097:blood / Q000187:drug effects; D018655:Lymphocyte Count; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D015166:Monitoring, Immunologic / Q000379:methods; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D000074324:Ipilimumab; D017493:Leukocyte Common Antigens; C520704:tremelimumab