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Semin Oncol. 2015 Jun;42(3):466-73. doi: 10.1053/j.seminoncol.2015.02.008. Epub 2015 Feb 13.

Anti-PD-1 therapy in melanoma.

Author information

1
Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA.
2
Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA; Department of Oncology, Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
3
Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA; Department of Surgery, University of California Los Angeles (UCLA), Los Angeles, CA; Department of Medical and Molecular Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA; Jonsson Comprehensive Cancer Center (JCCC) at UCLA, Los Angeles, CA. Electronic address: aribas@mednet.ucla.edu.

Abstract

Immune-regulatory mechanisms are used by cancer to hide from the immune system. Advances and in-depth understanding of the biology of melanoma and its interaction with the immune system have led to the development of some of antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its ligands, programmed death ligand 1 (PD-L1), which are demonstrating high clinical benefit rates and tolerability. Blocking the immune-regulatory checkpoints that limit T-cell responses to melanoma upon PD-1/PD-L1 modulation has provided clinically validated targets for cancer immunotherapy. Combinations with other anti-melanoma agents may result in additional benefits. Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers. Long-term survivors already have been reported with these therapies. In this review, we discuss the current state of anti-PD-1 agents, the evidence in the literature to support the combination of anti-PD-1 antibodies with other anti-cancer agents and discuss the future directions for rational design of clinical trials that keep on increasing the number of long-term survivors.

[Indexed for MEDLINE]

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