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一种突变型白细胞介素 2 的疗效和抗肿瘤活性。

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

机构信息

Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, 1316543551, Tehran, Iran.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

出版信息

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.

摘要

白细胞介素-2 (IL-2) 是一种重要的细胞因子,在黑色素瘤和肾细胞癌的免疫治疗中,它能促进 CD8+T 细胞和自然杀伤细胞的存活、扩增和功能。然而,由于其与高亲和力白细胞介素-2 受体 alpha(IL-2Rα)结合后会产生严重的毒性,限制了其在癌症患者中的应用。在本研究中,我们研究了一种先前通过选择性氨基酸取代设计的突变人白细胞介素-2 的抗肿瘤疗效和细胞毒性,与野生型白细胞介素-2(wtIL-2)相比,其对高亲和力白细胞介素-2 受体 alpha(CD25)的亲和力降低。此外,我们还比较了它们诱导 PBMC 细胞增殖和干扰素-γ分泌的能力。与野生型 hIL-2 相比,该突变白细胞介素-2 也表现出更高的抗肿瘤活性和更有效的细胞毒性。因此,开发的突变白细胞介素-2 可以作为 IL-2 相关免疫治疗各种癌症的替代工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a2/8968711/4b88f42f5607/41598_2022_9278_Fig1_HTML.jpg

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