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면역 미생물 공생 연구단
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TCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity

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dc.contributor.authorJun-Young Lee-
dc.contributor.authorLee, E-
dc.contributor.authorSung-Wook Hong-
dc.contributor.authorDaeun Kim-
dc.contributor.authorO. Eunju-
dc.contributor.authorSprent, J-
dc.contributor.authorSin-Hyeog Im-
dc.contributor.authorYou Jeong Lee-
dc.contributor.authorCharles D. Surh-
dc.date.accessioned2021-01-13T05:30:07Z-
dc.date.accessioned2021-01-13T05:30:07Z-
dc.date.available2021-01-13T05:30:07Z-
dc.date.available2021-01-13T05:30:07Z-
dc.date.created2019-11-18-
dc.date.issued2020-11-
dc.identifier.issn2162-402X-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/9053-
dc.description.abstractIL-2 is a pleiotropic cytokine that plays an essential role in the survival, expansion, and function of CD8 T cells, regulatory T cells (Tregs), and natural killer (NK) cells. Previous studies showed that binding IL-2 with an anti-IL-2 monoclonal antibody (mAb) with a particular specificity could block its interaction with IL-2R alpha, which is mainly expressed on Tregs. This selectivity can enhance the anti-tumor effects of IL-2 by activating CD8 T and NK cells, while disfavoring Treg stimulation. Based on this, we newly developed a series of anti-human IL-2 (hIL-2) mAbs (TCB1-3) that selectively stimulate CD8 T and NK cells without overtly activating Tregs. Among them, the hIL-2/TCB2 complex (hIL-2/TCB2c) exerted the best efficacy by inducing a prodigious expansion of host memory phenotype (MP) CD8 T (60-fold) and NK cells (18-fold) with less efficient Treg proliferation (5-fold). As a result, there was an average eightfold increase in the ratio of MP CD8 to Tregs. Accordingly, hIL-2/TCB2c strongly inhibited the growth of B16F10, MC38, and CT26 tumors. More remarkably, hIL-2/TCB2c showed synergy with checkpoint inhibitors such as anti-CTLA-4 or PD1 antibodies, and resulted in almost complete regression of implanted tumors and resistance to secondary tumor challenge. For direct clinical use, we generated a humanized form of TCB2 that had equal immunostimulatory and anti-tumor efficacy as a murine one. Collectively, these results show that TCB2 can provide a potent immunotherapeutic modality either alone or together with checkpoint inhibitors in cancer patients-
dc.description.uri1-
dc.language영어-
dc.publisherTAYLOR & FRANCIS INC-
dc.titleTCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000494056800001-
dc.identifier.scopusid2-s2.0-85076565105-
dc.identifier.rimsid70578-
dc.contributor.affiliatedAuthorJun-Young Lee-
dc.contributor.affiliatedAuthorSung-Wook Hong-
dc.contributor.affiliatedAuthorDaeun Kim-
dc.contributor.affiliatedAuthorO. Eunju-
dc.contributor.affiliatedAuthorSin-Hyeog Im-
dc.contributor.affiliatedAuthorYou Jeong Lee-
dc.contributor.affiliatedAuthorCharles D. Surh-
dc.identifier.doi10.1080/2162402X.2019.1681869-
dc.identifier.bibliographicCitationONCOIMMUNOLOGY, v.9, no.1, pp.1 - 12-
dc.citation.titleONCOIMMUNOLOGY-
dc.citation.volume9-
dc.citation.number1-
dc.citation.startPage1-
dc.citation.endPage12-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.subject.keywordPlusSELECTIVE STIMULATION-
dc.subject.keywordPlusIMMUNOTHERAPY-
dc.subject.keywordPlusCYTOKINE-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusBINDING-
dc.subject.keywordPlusDESIGN-
dc.subject.keywordAuthorIL-2-
dc.subject.keywordAuthorTCB2-
dc.subject.keywordAuthorcytokine-antibody complex-
dc.subject.keywordAuthorimmunotherapy-
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 1. Journal Papers (저널논문)
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