title: Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications.
abstract: Available medical treatments have limited impact on the survival of patients with advanced cancer; therefore, new therapeutic strategies able to generate more effective host's immune responses against neoplastic cells are being actively pursued. Among these, a recent approach involves targeting of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key immune checkpoint molecule, by monoclonal antibodies (mAbs). Ipilimumab and tremelimumab represent the prototypes of this new class of immunomodulating mAb and have been extensively tested in metastatic melanoma with highly promising results. The clinical activity observed in melanoma has served as a model to exploit the therapeutic potential of CTLA-4 blockade in a variety of human malignancies. Along this line, early-phase trials with anti-CTLA-4 mAbs have been completed or are ongoing in tumors of different histotype. Results are demonstrating the feasibility, safety, and activity of these agents, thus suggesting a promising therapeutic role to be further investigated in phase II/III trials in a wide range of tumors. This review summarizes the main trials with ipilimumab and tremelimumab in tumors of different histotypes, excluding cutaneous melanoma, which is extensively described in other chapters of this issue of Seminars in Oncology.
authors.affiliation: Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. l.calabro@ao-siena.toscana.it
authors.forename: Luana
authors.initials: L
authors.lastname: Calabrò
authors.forename: Riccardo
authors.initials: R
authors.lastname: Danielli
authors.forename: Luca
authors.initials: L
authors.lastname: Sigalotti
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D060908:CTLA-4 Antigen; D004067:Digestive System Neoplasms / Q000188:drug therapy; D005134:Eye Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008654:Mesothelioma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014565:Urogenital Neoplasms / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; C520704:tremelimumab