4.5 Review

Checkpoint blocking antibodies in cancer immunotherapy

Journal

FEBS LETTERS
Volume 588, Issue 2, Pages 368-376

Publisher

WILEY
DOI: 10.1016/j.febslet.2013.10.015

Keywords

Cytotoxic T-lymphocyte antigen 4; Programmed death-1 receptor; Immunotherapy; Checkpoint blocking antibodies; Malignancy

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Cancers can be recognized by the immune system, and the immune system may regulate and even eliminate tumors. The development of checkpoint blocking antibodies, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death 1 receptor (PD-1), have demonstrated significant recent promise in the treatment of an expanding list of malignancies. While both CTLA-4 and PD-1 function as negative regulators, each plays a non-redundant role in modulating immune responses. CTLA-4 attenuates the early activation of nave and memory T cells. In contrast, PD-1 is primarily involved in modulating T cell activity in peripheral tissues via interaction with its ligands, PD-L1 and PD-L2. Unfortunately, not all patients respond to these therapies, and evaluation of biomarkers associated with clinical outcomes is ongoing. This review will examine the efficacy, toxicities, and clinical development of checkpoint blocking antibodies, including agents already approved by the US Food and Drug Administration (anti-CTLA-4, ipilimumab) or in development (anti-PD-1, PD-L1). Future studies will likely uncover new promising immunologic checkpoints to target alone or in combination with other immunotherapeutic approaches, chemotherapy, radiotherapy, and small molecules. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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