title: Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
abstract: Cytotoxic T lymphocyte antigen-4 has become recognized as one of the key negative regulators of adaptive immune responses, having a central role in the maintenance of peripheral tolerance and in shaping the repertoire of emergent T cell responses. Concurrent recognition of the potential importance of inhibitory immune regulators in limiting antitumor responses, either as a result of chronic antigenic stimulation or the self-nature of many tumor-selective target antigens, has led to the development of cytotoxic T lymphocyte antigen-4-blocking antibodies as therapeutic anticancer agents. Following extensive preclinical modeling, these agents have entered clinical trials, where they are showing encouraging activity in heavily pretreated patients with advanced-stage disease, particularly with melanoma or renal carcinoma. Finding ways to dissociate antitumor activity from adverse immune events should enable actualization of their therapeutic potential in the coming years.
authors.affiliation: Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Quezada
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Korman
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000187:drug effects / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000276:immunology*; D060908:CTLA-4 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human