OncoTargets and Therapy (Mar 2016)
Tremelimumab: research and clinical development
Abstract
Begoña Comin-Anduix,1,2 Helena Escuin-Ordinas,3 Francisco Javier Ibarrondo4 1Division of Surgical-Oncology, Department of Surgery, 2Jonsson Comprehensive Cancer Center, 3Division of Hematology-Oncology, 4Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA Abstract: The immune checkpoint therapy is a relatively recent strategy that aims to tweak the immune system to effectively attack cancer cells. The understanding of the immune responses and their regulation at the intracellular level and the development of fully humanized monoclonal antibodies are the pillars of an approach that could elicit durable clinical responses and even remission in some patients with cancer. Most of the immune checkpoints that regulate the T-cell responses (activation and inhibition) operate through proteins present on the cytoplasmic membrane of the immune cells. Therefore, specific antibodies capable of blocking the inhibitory signals should lead to unrestrained immune responses that supersede the inhibitory mechanisms, which are naturally present in the tumor microenviroment. The best-known and most successful targets for immune checkpoint therapy are the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 coreceptors. Tremelimumab (CP-675,206) is a fully humanized monoclonal antibody specific for cytotoxic T-lymphocyte antigen-4, which has been successfully used to treat patients with metastatic melanoma and some other cancers. Although still a work in progress, the use of tremelimumab as an immune checkpoint therapeutic agent is a promising approach alone or in combination with other anticancer drugs. Here, we review the use of this antibody in a number of clinical trials against solid tumors. Keywords: immune checkpoint, anti-CTLA-4 blockade antibody, cancer
