DC Field | Value | Language |
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dc.contributor.author | Lee, Jun-Young | - |
dc.contributor.author | Lee, Eunjin | - |
dc.contributor.author | Hong, Sung Wook | - |
dc.contributor.author | Kim, Daeun | - |
dc.contributor.author | Eunju, O. | - |
dc.contributor.author | Sprent, Jonathan | - |
dc.contributor.author | Im, Sin-Hyeog | - |
dc.contributor.author | Lee, You Jeong | - |
dc.contributor.author | Surh, Charles D. | - |
dc.date.accessioned | 2020-02-12T06:50:04Z | - |
dc.date.available | 2020-02-12T06:50:04Z | - |
dc.date.created | 2019-11-20 | - |
dc.date.issued | 2019-11 | - |
dc.identifier.issn | 2162-402X | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/100895 | - |
dc.description.abstract | IL-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.language | English | - |
dc.publisher | TAYLOR & FRANCIS INC | - |
dc.relation.isPartOf | ONCOIMMUNOLOGY | - |
dc.title | TCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity | - |
dc.type | Article | - |
dc.identifier.doi | 10.1080/2162402X.2019.1681869 | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | ONCOIMMUNOLOGY, v.9, no.1 | - |
dc.identifier.wosid | 000494056800001 | - |
dc.citation.number | 1 | - |
dc.citation.title | ONCOIMMUNOLOGY | - |
dc.citation.volume | 9 | - |
dc.contributor.affiliatedAuthor | Lee, Jun-Young | - |
dc.contributor.affiliatedAuthor | Lee, Eunjin | - |
dc.contributor.affiliatedAuthor | Kim, Daeun | - |
dc.contributor.affiliatedAuthor | Im, Sin-Hyeog | - |
dc.contributor.affiliatedAuthor | Lee, You Jeong | - |
dc.identifier.scopusid | 2-s2.0-85076565105 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.type.docType | Article; Early Access | - |
dc.subject.keywordPlus | SELECTIVE STIMULATION | - |
dc.subject.keywordPlus | IMMUNOTHERAPY | - |
dc.subject.keywordPlus | CYTOKINE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordAuthor | IL-2 | - |
dc.subject.keywordAuthor | TCB2 | - |
dc.subject.keywordAuthor | cytokine-antibody complex | - |
dc.subject.keywordAuthor | immunotherapy | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Immunology | - |
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