Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
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.
Peggs
Karl S
KS
Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Quezada
Sergio A
SA
Korman
Alan J
AJ
Allison
James P
JP
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*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human