Efficacy and antitumor activity of a mutant type of interleukin 2

Sci Rep. 2022 Mar 30;12(1):5376. doi: 10.1038/s41598-022-09278-7.

Abstract

Interleukin-2 (IL-2) is an important cytokine in survival, expansion, function of CD8+ T cells and natural killer cells in immunotherapy of melanoma and renal cell carcinomas. Its severe toxicity following binding to its high affinity IL-2 receptor alpha (IL-2Rα) has restricted its application in cancer patients. In the present study, we investigated the antitumor efficacy and cytotoxicity of a mutated human IL-2 previously designed by selective amino acid substitutions, and its reduced affinity towards high-affinity IL-2Rα (CD25) was approved compared to the wild type IL-2 (wtIL-2). Furthermore, their ability to induce PBMC cell proliferation, and interferon-gamma secretion was compared. The mutant IL-2 also represented higher antitumor activity and more efficient cytotoxicity than wild type hIL-2. The developed mutant IL-2 can be an alternative tool in IL-2 associated immunotherapy of various cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Interleukin-2* / genetics
  • Interleukin-2* / metabolism
  • Interleukin-2* / pharmacology
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Melanoma* / metabolism
  • Receptors, Interleukin-2 / metabolism

Substances

  • Interleukin-2
  • Receptors, Interleukin-2