title: Immunotherapy for malignant melanoma.
abstract: Treatment of metastatic melanoma is a challenge for clinicians as most agents have failed to demonstrate improved survival in phase III trials. Despite the immunogenicity of this tumor entity, different immunological interventions including cytokine therapy, vaccination, biochemotherapy or allogeneic hematopoietic cell transplantation did not lead to a satisfactory response. However, continuous investigation on the immune mediated rejection of melanoma cells has led to the development of effective antibodies blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4), a critical negative regulator of the antitumor T-cell response. Based on data from rodent models, the anti-CTLA-4 antibody ipilimumab was developed into clinical studies where it had encouraging activity in advanced melanoma with unusual response patterns. As in most immunostimulatory therapies, acute toxicities were severe and clearly mechanism-related. Although some patients developed signs of autoimmunity, the toxicities were overall manageable and mostly reversible. This review summarizes different immunotherapeutical approaches against melanoma that have been applied in the past and focuses on CTLA-4 blockade with respect to its mechanism, clinical effectiveness and immunological side effects.
authors.affiliation: Department of Hematology and Oncology, Freiburg University Medical Center, Albert Ludwigs University, Freiburg, Germany. robert.zeiser@uniklinik-freiburg.de
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.forename: Marc
authors.initials: M
authors.lastname: Schnitzler
authors.forename: Hana
authors.initials: H
authors.lastname: Andrlova
authors.forename: Tina
authors.initials: T
authors.lastname: Hellige
authors.forename: Frank
authors.initials: F
authors.lastname: Meiss
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D016207:Cytokines / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; D000074324:Ipilimumab