Update on anti-CTLA-4 antibodies in clinical trials.
Breaking immune tolerance against tumor self-antigens is presently an area of intense research in the design of cancer therapies. One possible method to enhance immune system activation against tumor antigens is by blocking the inhibitory co-stimulatory signals mediated by cytotoxic T lymphocyte antigen 4, (CTLA-4) expressed on activated T cells. The fully human monoclonal antibodies that are directed against human CTLA-4, ipilimumab (Medarex/Bristol-Myers Squibb) and CP-675,206 (Pfizer/Abgenix, now Amgen), have demonstrated activity against metastatic melanoma, hormone refractory prostate cancer and other malignancies. They have also uncovered unusual immune-related adverse events manifesting as self-limiting inflammatory reactions of the bowel, skin and pituitary. This article reviews preclinical development and data generated from Phase I, II and III studies with regard to the end points reported and immune-related adverse events.
Langer
Lee F
LF
Duke University Medical Center, Department of Surgery, Program in Molecular Therapeutics, Comprehensive Cancer Center, Durham, NC 27710, USA.
Clay
Timothy M
TM
Morse
Michael A
MA
D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000627:therapeutic use*; D000943:Antigens, Differentiation / Q000276:immunology* / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods
D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human