A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Joong-Jae | - |
dc.contributor.author | Kim, Hyun Jung | - |
dc.contributor.author | Yang, Chul-Su | - |
dc.contributor.author | Kyeong, Hyun-Ho | - |
dc.contributor.author | Choi, Jung-Min | - |
dc.contributor.author | Hwang, Da-Eun | - |
dc.contributor.author | Yuk, Jae-Min | - |
dc.contributor.author | Park, Keunwan Department of Bio and Brai | - |
dc.contributor.author | Kim, Yu Jung | - |
dc.contributor.author | Lee, Seung-Goo | - |
dc.contributor.author | Kim, Dongsup | - |
dc.contributor.author | Jo, Eun-Kyeong | - |
dc.contributor.author | Cheong, Hae-Kap | - |
dc.contributor.author | Kim, Hak-Sung | - |
dc.date.accessioned | 2021-06-23T01:23:58Z | - |
dc.date.available | 2021-06-23T01:23:58Z | - |
dc.date.issued | 2014-07 | - |
dc.identifier.issn | 1525-0016 | - |
dc.identifier.issn | 1525-0024 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/25454 | - |
dc.description.abstract | Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune responses for host defense and tumorigenic process. Upregulation of IL-6 is known to constitutively phosphorylate signal transducer and activator of transcription 3 (STAT3), leading to activation of multiple oncogene pathways and inflammatory cascade. Here, we present the development of a high-affinity protein binder, termed repebody, which effectively suppresses non-small cell lung cancer in vivo by blocking the IL-6/STAT3 signaling. We selected a repebody that prevents human IL-6 (hIL-6) from binding to its receptor by a competitive immunoassay, and modulated its binding affinity for hIL-6 up to a picomolar range by a modular approach that mimics the combinatorial assembly of diverse modules to form antigen-specific receptors in nature. The resulting repebody was highly specific for hIL-6, effectively inhibiting the STAT3 phosphorylation in a dose- and binding affinity-response manner in vitro. The repebody was shown to have a remarkable suppression effect on the growth of tumors and STAT3 phosphorylation in xenograft mice with non-small cell lung cancer by blocking the hIL-6/STAT3 signaling. Structural analysis of the repebody and IL-6 complex revealed that the repebody binds the site 2a of hIL-6, overlapping a number of epitope residues at site 2a with gp130, and consequently causes a steric hindrance to the formation of IL-6/IL-6Rα complex. Our results suggest that high-affinity repebody targeting the IL-6/STAT3 pathway can be developed as therapeutics for non-small cell lung cancer. © The American Society of Gene & Cell Therapy. | - |
dc.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1038/mt.2014.59 | - |
dc.identifier.scopusid | 2-s2.0-84903763186 | - |
dc.identifier.wosid | 000338189800006 | - |
dc.identifier.bibliographicCitation | Molecular Therapy, v.22, no.7, pp 1254 - 1265 | - |
dc.citation.title | Molecular Therapy | - |
dc.citation.volume | 22 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1254 | - |
dc.citation.endPage | 1265 | - |
dc.type.docType | Conference Paper | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biotechnology & Applied Microbiology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biotechnology & Applied Microbiology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | antineoplastic agent | - |
dc.subject.keywordPlus | interleukin 6 | - |
dc.subject.keywordPlus | repebody | - |
dc.subject.keywordPlus | STAT3 protein | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | antineoplastic agent | - |
dc.subject.keywordPlus | interleukin 6 | - |
dc.subject.keywordPlus | STAT3 protein | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | animal model | - |
dc.subject.keywordPlus | binding affinity | - |
dc.subject.keywordPlus | binding site | - |
dc.subject.keywordPlus | cancer inhibition | - |
dc.subject.keywordPlus | concentration response | - |
dc.subject.keywordPlus | conference paper | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | crystal structure | - |
dc.subject.keywordPlus | drug effect | - |
dc.subject.keywordPlus | drug efficacy | - |
dc.subject.keywordPlus | drug mechanism | - |
dc.subject.keywordPlus | drug protein binding | - |
dc.subject.keywordPlus | drug targeting | - |
dc.subject.keywordPlus | female | - |
dc.subject.keywordPlus | immunoassay | - |
dc.subject.keywordPlus | in vitro study | - |
dc.subject.keywordPlus | in vivo study | - |
dc.subject.keywordPlus | lung non small cell cancer | - |
dc.subject.keywordPlus | molecular evolution | - |
dc.subject.keywordPlus | mouse | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | protein phosphorylation | - |
dc.subject.keywordPlus | signal transduction | - |
dc.subject.keywordPlus | animal | - |
dc.subject.keywordPlus | Carcinoma, Non-Small-Cell Lung | - |
dc.subject.keywordPlus | drug effects | - |
dc.subject.keywordPlus | drug screening | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | metabolism | - |
dc.subject.keywordPlus | nude mouse | - |
dc.subject.keywordPlus | signal transduction | - |
dc.subject.keywordPlus | Mus | - |
dc.subject.keywordPlus | Animals | - |
dc.subject.keywordPlus | Antineoplastic Agents | - |
dc.subject.keywordPlus | Carcinoma, Non-Small-Cell Lung | - |
dc.subject.keywordPlus | Female | - |
dc.subject.keywordPlus | Humans | - |
dc.subject.keywordPlus | Interleukin-6 | - |
dc.subject.keywordPlus | Mice | - |
dc.subject.keywordPlus | Mice, Nude | - |
dc.subject.keywordPlus | Signal Transduction | - |
dc.subject.keywordPlus | STAT3 Transcription Factor | - |
dc.subject.keywordPlus | Xenograft Model Antitumor Assays | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1525001616307171?via%3Dihub | - |
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