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FEBS Lett. 2014 Jan 21;588(2):368-76. doi: 10.1016/j.febslet.2013.10.015. Epub 2013 Oct 23.

Checkpoint blocking antibodies in cancer immunotherapy.

Author information

1
Department of Medicine, New York Presbyterian Hospital Cornell, 525 E 68th St., New York, NY 10065, United States.
2
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 E 66th St., New York, NY 10065, United States. Electronic address: PostowM@mskcc.org.

Abstract

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 naïve 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.

KEYWORDS:

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

PMID:
24161671
DOI:
10.1016/j.febslet.2013.10.015
[Indexed for MEDLINE]
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