Efficacy and antitumor activity of a mutant type of interleukin 2.

Rada Dehghan, Arezoo Beig Parikhani, Sirous Zeinali, Mohamadali Shokrgozar, Amir Amanzadeh, Soheila Ajdary, Reza Ahangari Cohan, Yeganeh Talebkhan, Mahdi Behdani

Scientific reports 2022 Mar 30

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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. © 2022. The Author(s).

Citation

Rada Dehghan, Arezoo Beig Parikhani, Sirous Zeinali, Mohamadali Shokrgozar, Amir Amanzadeh, Soheila Ajdary, Reza Ahangari Cohan, Yeganeh Talebkhan, Mahdi Behdani. Efficacy and antitumor activity of a mutant type of interleukin 2. Scientific reports. 2022 Mar 30;12(1):5376