DC Field | Value | Language |
---|---|---|
dc.contributor.author | Carmenate, Tania | - |
dc.contributor.author | Montalvo, Galia | - |
dc.contributor.author | Lozada, Sum Lai | - |
dc.contributor.author | Rodriguez, Yaretnis | - |
dc.contributor.author | Ortiz, Yaquelin | - |
dc.contributor.author | Díaz, Claudia | - |
dc.contributor.author | Avellanet, Janet | - |
dc.contributor.author | Kim, Juhee | - |
dc.contributor.author | Surh, Charles D. | - |
dc.contributor.author | Graça, Luis | - |
dc.contributor.author | León, Kalet | - |
dc.date.accessioned | 2023-07-11T01:42:00Z | - |
dc.date.available | 2023-07-11T01:42:00Z | - |
dc.date.created | 2022-12-22 | - |
dc.date.issued | 2022-08 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/117892 | - |
dc.description.abstract | Copyright © 2022 Carmenate, Montalvo, Lozada, Rodriguez, Ortiz, Díaz, Avellanet, Kim, Surh, Graça and León.High doses of interleukin-2 (IL-2) have been used for the treatment of melanoma and renal cell carcinoma, but this therapy has limited efficacy, with a ~15% response rate. Remarkably, 7%–9% of patients achieve complete or long-lasting responses. Many patients treated with IL-2 experienced an expansion of regulatory T cells (Tregs), specifically the expansion of ICOS+ highly suppressive Tregs, which correlate with worse clinical outcomes. This partial efficacy together with the high toxicity associated with the therapy has limited the use of IL-2-based therapy. Taking into account the understanding of IL-2 structure, signaling, and in vivo functions, some efforts to improve the cytokine properties are currently under study. In previous work, we described an IL-2 mutein with higher antitumor activity and less toxicity than wtIL-2. Mutein was in silico designed for losing the binding capacity to CD25 and for preferential stimulation of effector cells CD8+ and NK cells but not Tregs. Mutein induces a higher anti-metastatic effect than wtIL-2, but the extent of the in vivo antitumor activity was still unexplored. In this work, it is shown that mutein induces a strong antitumor effect on four primary tumor models, being effective even in those models where wtIL-2 does not work. Furthermore, mutein can change the in vivo balance between Tregs and T CD8+ memory/activated cells toward immune activation, in both healthy and tumor-bearing mice. This change reaches the tumor microenvironment and seems to be the major explanation for mutein efficacy in vivo. | - |
dc.language | English | - |
dc.publisher | Frontiers Media S.A. | - |
dc.relation.isPartOf | Frontiers in Immunology | - |
dc.title | The antitumor effect induced by an IL-2 ‘no-alpha’ mutein depends on changes in the CD8+ T lymphocyte/Treg cell balance | - |
dc.type | Article | - |
dc.identifier.doi | 10.3389/fimmu.2022.974188 | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | Frontiers in Immunology, v.13 | - |
dc.identifier.wosid | 000848532600001 | - |
dc.citation.title | Frontiers in Immunology | - |
dc.citation.volume | 13 | - |
dc.contributor.affiliatedAuthor | Kim, Juhee | - |
dc.contributor.affiliatedAuthor | Surh, Charles D. | - |
dc.identifier.scopusid | 2-s2.0-85137250787 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | INTERLEUKIN-2 | - |
dc.subject.keywordPlus | DEPLETION | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordAuthor | cancer therapy | - |
dc.subject.keywordAuthor | CD8+ T cells | - |
dc.subject.keywordAuthor | IL-2 mutein | - |
dc.subject.keywordAuthor | TME | - |
dc.subject.keywordAuthor | treg | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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