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

  • Cytokine Growth Factor Rev. 2017 Dec;38:10-21. doi: 10.1016/j.cytogfr.2017.08.002.
Yin Guo  1 ,  Liming Luan  2 ,  Naeem K Patil  2 ,  Edward R Sherwood  3
Affiliations
  • 1. Departments of Pathology, Microbiology and Immunology. Vanderbilt University, Nashville, TN, USA; Department of Anesthesiology. Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: [email protected].
  • 2. Department of Anesthesiology. Vanderbilt University Medical Center, Nashville, TN, USA.
  • 3. Departments of Pathology, Microbiology and Immunology. Vanderbilt University, Nashville, TN, USA; Department of Anesthesiology. Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: [email protected].
PMID: 28888485 DOI: 10.1016/j.cytogfr.2017.08.002
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 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 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 Rα 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.

Keywords
Anti-viral immunotherapy; Cancer immunotherapy; IL-15 superagonist; IL-15 trans-presentation; Memory CD8 T lymphocytes; Natural killer cells.
Products