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Nivolumab

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Immunotherapy of Melanoma

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Abstract

Nivolumab belongs to the class of check point blockers that showed enormous potential in the treatment of melanoma. Its use as a monotherapy was approved by US FDA for the treatment of metastatic melanoma in December 2014 and its combination with ipilimumab was approved in September 2015. Nivolumab is a monoclonal antibody against the PD-1 receptor. PD-1 belongs to the immunoglobulin superfamily of proteins and is expressed on the cell surface of T- and B-cells in response to inflammatory signals in the tumor microenvironment. Upon binding with its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC), it generates a ‘negative’ signal inside T-cells and results in inhibition of T-cell functions. The current chapter describes the PD-1 receptors and the clinical potential of PD-1 blocker nivolumab. In the introduction section of the chapter, the discovery of PD-1 receptors and the phenotype of PD-1 deficient mice (Pdcd −/− mice) are described. Next, the structure of PD-1 receptor, its biology and the signaling events that follow the activation of PD-1 receptor are explained. After giving a brief description of Opdivo, the marketed formulation of nivolumab, its clinical pharmacology and mechanism of action at cellular level is described. The details of clinical trials that tested the use of nivolumab in melanoma patients and the adverse effects, drug interactions as well as contraindications of nivolumab are then discussed. In the end, the limitations of using nivolumab are described.

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  1. Faculty of Medicine, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada

    Anand Rotte & Madhuri Bhandaru

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  1. Anand Rotte
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  2. Madhuri Bhandaru
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Rotte, A., Bhandaru, M. (2016). Nivolumab. In: Immunotherapy of Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-48066-4_12

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