Back to Journals » Clinical, Cosmetic and Investigational Dermatology » Volume 6

Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

Authors Tosti G, Cocorocchio E, Pennacchioli E

Received 26 July 2013

Accepted for publication 2 September 2013

Published 17 October 2013 Volume 2013:6 Pages 245—256

DOI https://doi.org/10.2147/CCID.S24246

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4


Giulio Tosti, Emilia Cocorocchio, Elisabetta Pennacchioli

Divisione Melanomi e Sarcomi, Istituto Europeo di Oncologia, Milano, Italy

Abstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under investigation in combination with other treatments, such as chemotherapy, target agents, radiotherapy, and other immunotherapeutic regimens.

Keywords: CTLA-4, CTLA-4 blockade, ipilimumab, metastatic melanoma, immunotherapy

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]