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Immunobiology of the IL-15/IL-15R? complex as an antitumor and antiviral agent.


ABSTRACT: Interleukin (IL)-15 is essential for natural killer (NK), NKT and memory (m) CD8+ T cell development and function, and is currently under investigation as an immunotherapeutic agent for the treatment of cancer. Recently, the creation of IL-15 superagonist by complexing IL-15 and its high affinity receptor alpha (IL-15 R?) in solution, inspired by the natural trans-presentation of IL-15, advances the potential of IL-15-based tumor immunotherapy. IL-15 superagonist shows promising advantages over monomeric IL-15 such as sustaining high circulating concentrations due to prolonged half-life and more potently stimulating NK and CD8+ T effector lymphocytes. So far, there are three different forms of recombinant IL-15 superagonist fusion protein based on configurational modifications. Gene therapy using engineered cells co-expressing IL-15/IL-15 R? complex for cancer treatment is also emerging. All forms have demonstrated efficacy in causing tumor regression in animal studies, which provides strong rationale for advancing IL-15 superagonist through clinical trials. To date, there are fourteen phase I/II IL-15 superagonist trials in cancer patients and one phase I trial in HIV patients. Information generated by ongoing trials regarding the toxicity and efficacy of IL-15 superagonist is awaited. Finally, we elaborate on immunotoxicity caused by IL-15 superagonist in preclinical studies and discuss important safety considerations.

SUBMITTER: Guo Y 

PROVIDER: S-EPMC5705392 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent.

Guo Yin Y   Luan Liming L   Patil Naeem K NK   Sherwood Edward R ER  

Cytokine & growth factor reviews 20170901


Interleukin (IL)-15 is essential for natural killer (NK), NKT and memory (m) CD8<sup>+</sup> T cell development and function, and is currently under investigation as an immunotherapeutic agent for the treatment of cancer. Recently, the creation of IL-15 superagonist by complexing IL-15 and its high affinity receptor alpha (IL-15 Rα) in solution, inspired by the natural trans-presentation of IL-15, advances the potential of IL-15-based tumor immunotherapy. IL-15 superagonist shows promising advan  ...[more]

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