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Efficacy and antitumor activity of a mutant type of interleukin 2

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 ca...

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Autores principales: Dehghan, Rada, Beig Parikhani, Arezoo, Zeinali, Sirous, Shokrgozar, Mohamadali, Amanzadeh, Amir, Ajdary, Soheila, Ahangari Cohan, Reza, Talebkhan, Yeganeh, Behdani, Mahdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968711/
https://www.ncbi.nlm.nih.gov/pubmed/35354847
http://dx.doi.org/10.1038/s41598-022-09278-7
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author Dehghan, Rada
Beig Parikhani, Arezoo
Zeinali, Sirous
Shokrgozar, Mohamadali
Amanzadeh, Amir
Ajdary, Soheila
Ahangari Cohan, Reza
Talebkhan, Yeganeh
Behdani, Mahdi
author_facet Dehghan, Rada
Beig Parikhani, Arezoo
Zeinali, Sirous
Shokrgozar, Mohamadali
Amanzadeh, Amir
Ajdary, Soheila
Ahangari Cohan, Reza
Talebkhan, Yeganeh
Behdani, Mahdi
author_sort Dehghan, Rada
collection PubMed
description 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.
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spelling pubmed-89687112022-04-01 Efficacy and antitumor activity of a mutant type of interleukin 2 Dehghan, Rada Beig Parikhani, Arezoo Zeinali, Sirous Shokrgozar, Mohamadali Amanzadeh, Amir Ajdary, Soheila Ahangari Cohan, Reza Talebkhan, Yeganeh Behdani, Mahdi Sci Rep Article 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. Nature Publishing Group UK 2022-03-30 /pmc/articles/PMC8968711/ /pubmed/35354847 http://dx.doi.org/10.1038/s41598-022-09278-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Dehghan, Rada
Beig Parikhani, Arezoo
Zeinali, Sirous
Shokrgozar, Mohamadali
Amanzadeh, Amir
Ajdary, Soheila
Ahangari Cohan, Reza
Talebkhan, Yeganeh
Behdani, Mahdi
Efficacy and antitumor activity of a mutant type of interleukin 2
title Efficacy and antitumor activity of a mutant type of interleukin 2
title_full Efficacy and antitumor activity of a mutant type of interleukin 2
title_fullStr Efficacy and antitumor activity of a mutant type of interleukin 2
title_full_unstemmed Efficacy and antitumor activity of a mutant type of interleukin 2
title_short Efficacy and antitumor activity of a mutant type of interleukin 2
title_sort efficacy and antitumor activity of a mutant type of interleukin 2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968711/
https://www.ncbi.nlm.nih.gov/pubmed/35354847
http://dx.doi.org/10.1038/s41598-022-09278-7
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