title: Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management.
abstract: Immune-modifying monoclonal antibodies may induce or enhance the natural immune response against tumor cells. The complex interaction between antigen-presenting cells and T lymphocytes as an immune response is strongly affected by anti-CD152 (cytotoxic T-lymphocyte antigen-4, CTLA-4)-antibodies. However, specific CTLA-4 antibodies can block the CTLA-4 receptor and thus induce an unrestrained T-cell activation. To this stage, treatment of patients with metastatic melanoma with the CTLA-4 antibodies ipilimumab and tremelimumab has only been investigated within clinical trials. The results of a phase III trial in patients with advanced disease treated with ipilimumab alone or in combination with a peptide vaccination (gp100) recently presented at the 2010 annual meeting of the Ameircan Society of Clinical Oncology (ASCO) made groundbreaking news as ipilimumab was demonstrated to be the first drug in melanoma treatment to show a significant prolongation of survival time. Patients undergoing treatment with CTLA-4 antibodies may experience immune-related phenomena and adverse events (irAEs) that differ greatly from the well-known adverse events of cytotoxic drugs and which are due to the CTLA-4 antibodies' specific mode of action. This review gives a condensed overview on the mechanisms of action, an update on clinical data of the two CTLA-4 antibodies, ipilimumab and tremelimumab, and detailed recommendations for adverse event management strategies.
authors.affiliation: Department of Dermatology and Skin Cancer Center, University Hospital Schleswig-Holtstein, Campus Kiel, Germany.
authors.forename: Katharina C
authors.initials: KC
authors.lastname: Kaehler
authors.forename: Sarah
authors.initials: S
authors.lastname: Piel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Livingstone
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D060908:CTLA-4 Antigen; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000628:therapy; D004066:Digestive System Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D004700:Endocrine System Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D006801:Humans; D007154:Immune System Diseases / Q000139:chemically induced* / Q000628:therapy; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D012871:Skin Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000970:Antineoplastic Agents; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; D002097:C-Reactive Protein; C520704:tremelimumab