期刊
CYTOKINE & GROWTH FACTOR REVIEWS
卷 38, 期 -, 页码 10-21出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cytogfr.2017.08.002
关键词
Natural killer cells; Memory CD8 T lymphocytes; Cancer immunotherapy; IL-15 trans-presentation; IL-15 superagonist; Anti-viral immunotherapy
资金
- National Institutes of Health [R01 GM66885]
- American Heart Association Postdoctoral [16POST29920007]
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 alpha) 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 alpha 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.
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