Efficacy and antitumor activity of a mutant type of interleukin 2

• Published in: Scientific reports Vol. 12; no. 1; pp. 5376 - 7
• Main Authors: Dehghan, Rada, Beig Parikhani, Arezoo, Zeinali, Sirous, Shokrgozar, Mohamadali, Amanzadeh, Amir, Ajdary, Soheila, Ahangari Cohan, Reza, Talebkhan, Yeganeh, Behdani, Mahdi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/61; 631/67; Affinity; Amino acids; Antitumor activity; CD25 antigen; CD8 antigen; Cell proliferation; Cytokines; Cytotoxicity; Humanities and Social Sciences; Humans; Immunotherapy; Interleukin 2; Interleukin 2 receptors; Interleukin-2 - genetics; Interleukin-2 - metabolism; Interleukin-2 - pharmacology; Kidney cancer; Killer Cells, Natural - metabolism; Leukocytes, Mononuclear - metabolism; Lymphocytes T; Melanoma; Melanoma - metabolism; multidisciplinary; Mutants; Natural killer cells; Peripheral blood mononuclear cells; Receptors, Interleukin-2 - metabolism; Renal cell carcinoma; Science; Science (multidisciplinary); γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09278-7

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.