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Interleukin-2

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Immunotherapy of Melanoma

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Abstract

Interleukin-2 or IL-2 is a member of four-alpha helix bundle cytokine family that signals through IL-2 receptor and is one of the oldest cytokine to be discovered. It mainly functions as a T-cell growth factor. Its discovery is considered as a major milestone in the field of immunology and the cloning of its cDNA which allowed the production of recombinant IL-2 is considered as a turning point in immunology research. IL-2 is also one of the oldest cytokine to be tested for its use in the treatment of melanoma; its earliest use dates back to 1980s. Its use has been approved by US FDA for the treatment of patients with unresectable metastatic melanoma in 1998. In this chapter, the details of clinically used recombinant IL-2 including its structure, biology and pharmacology are discussed. First, the historical aspects of IL-2 discovery and generation of recombinant IL-2 are described followed by a brief note on the earliest recorded use of IL-2 in cancer patient. The structure of IL-2 protein and the variations introduced in the protein structure of clinically used IL-2 analog are described followed by description of the sequence of signaling events that occur due to the activation of IL-2 receptor. Next, the details of preclinical and clinical trials that demonstrated the potential of IL-2 in the treatment of metastatic melanoma, the description of aldesleukin (recombinant IL-2 formulation that is available in the market), clinical pharmacology, mechanism of action, adverse effects, drug interactions, contraindications and limitations are discussed.

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Authors and Affiliations

  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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Correspondence to Anand Rotte .

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Rotte, A., Bhandaru, M. (2016). Interleukin-2. In: Immunotherapy of Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-48066-4_10

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