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Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application

Paolo A Ascierto1*, Francesco M Marincola2 and Antoni Ribas3

Author Affiliations

1 Unit of Medical Oncology and Innovative Therapies, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy

2 Infectious Diseases and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA

3 Department of Medicine, Jonsson Comprehensive Cancer Center at the University of California Los Angeles (UCLA), Los Angeles, California, USA

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Journal of Translational Medicine 2011, 9:196  doi:10.1186/1479-5876-9-196

Published: 13 November 2011


Recently, two studies using ipilimumab, an anti-CTLA-4 monoclonal antibody (mab) demonstrated improvements in overall survival in the treatment of advanced melanoma. These studies utilized two different schedules of treatment in different patient categories (first and second line of treatment). However, the results were quite similar despite of different dosage used and the combination with dacarbazine in the first line treatment. We reviewed the result of randomized phase II-III clinical studies testing anti-CTLA-4 antibodies (ipilimumab and tremelimumab) for the treatment of melanoma to focus on practical or scientific questions related to the broad utilization of these products in the clinics. These analyses raised some considerations about the future of these compounds, their potential application, dosage, the importance of the schedule (induction/manteinance compared to induction alone) and their role as adjuvants. Anti-CTLA-4 antibody therapy represents the start of a new era in the treatment of advanced melanoma but we are on the steep slope of the learning curve toward the optimization of their utilization either a single agents or in combination.