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dc.contributor.authorChen, X.
dc.contributor.authorAi, X.
dc.contributor.authorWu, C.
dc.date.accessioned2019-05-17T13:21:18Z
dc.date.available2019-05-17T13:21:18Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85053807747&doi=10.1038%2fs41419-018-1047-2&partnerID=40&md5=c0c4b174eaaf73f077042d924203cef7
dc.identifier.urihttp://hdl.handle.net/10713/9215
dc.description.abstractIL-2 is critical to the activation, growth, and survival of T cells and NK cells, and maintains the delicate balance between auto-immunity and anti-neoplasm surveillance. High IL-2 doses have clear antitumor capabilities, but also have severe side effects that limit its clinical use. Side effects include the vascular leak syndrome (VLS), which results in lung edema and liver damage. Therefore, a new version of IL-2 that does not induce organ toxicity would improve IL-2-based immunotherapy. We conducted a systematic screening by changing one amino acid at a time at the interaction area of IL-2 with its receptor IL-2R to select one particular mutant IL-2, FSD13, in which the proline at position 65 was substituted by lysine (P65L). FSD13 had a greater ability than wild-type IL-2 in stimulating CD4 + T, CD8 + T, and NK cell proliferation, enhancing the expression of CD69, CD183, CD44, and CD54 in these cells, and triggering cancer cell apoptosis. FSD13 had three-time lower than wild-type IL-2 in inducing CD4 + T to Tregs. Compared with wild-type IL-2, FSD13 greatly limited the growth, invasion into adjacent tissues, and metastasis of melanoma metastatic into the lung. In contrast to wild-type IL-2, high dose of FSD3 did not alter structures and induce any pathogenic changes in the liver and lung. Thus, we generated a novel the IL-2 mutant, FSD13, by targeting a different area than previously reported. FSD13 surpasses the wild-type IL-2's ability in stimulating the antitumor immune cell functions, but exerts much less systemic toxicity. Copyright 2018, The Author(s).en_US
dc.description.sponsorshipThis work was supported in part by grants from the National Natural Science Foundation of China (Numbers 81272433, 81328018, 81372300, 81472732 and 8177315).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41419-018-1047-2en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofCell Death and Disease
dc.subject.meshAmino Acid Sequence--geneticsen_US
dc.subject.meshInterleukin-2--geneticsen_US
dc.subject.meshInterleukin-2--immunologyen_US
dc.subject.meshNeoplasms--immunologyen_US
dc.titleA novel human IL-2 mutein with minimal systemic toxicity exerts greater antitumor efficacy than wild-type IL-2en_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41419-018-1047-2
dc.identifier.pmid30250191


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