title: Ipilimumab targeting CD28-CTLA-4 axis: new hope in the treatment of melanoma.
abstract: Ipilimumab, a fully human monoclonal antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), is the new hope in the treatment of patients with advanced melanoma. Anti-CTLA-4 antibodies enhance T cell responses in vitro and in vivo and activate proliferation of tumour-specific T cells. The blockade of CTLA-4 by ipilimumab leads to immune-mediated tumor regression. Ipilimumab has been studied in metastatic melanoma in a number of clinical trials. Recently, a phase III, multi-center, randomized, double-blind trial showed a significant improvement in overall survival in patients with advanced melanomas treated with ipilimumab. Thus, ipilimumab was the first drug to demonstrate effect on overall survival in patients with metastatic melanoma. However, patients treated with ipilimumab develop various immune-related adverse events (irAEs), which are associated with objective and durable clinical responses. Use of new immune-related response criteria is recommended in patients on ipilimumab therapy to avoid premature treatment discontinuation. Further research is necessary to elucidate role of ipilimumab in adjuvant setting as well as in synergy with other novel modalities for the treatment of metastatic melanoma.
authors.affiliation: King's College, Genetic Epidemiology Unit, St.Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom. markolens@aol.com
authors.forename: Marko
authors.initials: M
authors.lastname: Lens
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Ferucci
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000074324:Ipilimumab; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab