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Heterodimeric Fc-fused IL12 shows potent antitumor activity by generating memory CD8(+) T cells

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dc.contributor.authorJung, K-
dc.contributor.authorHa, JH-
dc.contributor.authorKim, JE-
dc.contributor.authorKim, JA-
dc.contributor.authorKim, YJ-
dc.contributor.authorKim, CH-
dc.contributor.authorKim, YS-
dc.date.accessioned2019-11-13T00:18:13Z-
dc.date.available2019-11-13T00:18:13Z-
dc.date.issued2018-
dc.identifier.issn2162-4011-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/16919-
dc.description.abstractInterleukin-12 (IL12) (p35/p40 complex) is a heterodimeric cytokine with potent anti-tumor activity. However, its short serum half-life and high dose-related toxicities limit its clinical efficacy. Here, we constructed heterodimeric immunoglobulin Fc-fused mouse IL12 (mIL12) in a monovalent binding format (mono-mIL12-Fc) to generate long-acting mIL12 in the naturally occurring heterodimeric form. Mono-mIL12-Fc exhibited a much longer plasma half-life than recombinant mIL12, enabling twice-weekly systemic injections to remove established tumors in syngeneic mouse models. Mono-mIL12-Fc was more potent than wild-type Fc-based bivalent-binding IL12-Fc (bi-mIL12-Fc) for eradicating large established immunogenic tumors without noticeable toxicities by enhancing interferon-gamma production and the proliferation of immune effector cells in tumors. More importantly, mono-mIL12-Fc triggered weaker IL12 signaling than bi-mIL12-Fc, favoring the generation of functional and protective memory CD8(+) T cells. Our results demonstrate that heterodimeric-Fc-fused IL12 is a suitable format for augmenting adaptive CD8(+) T cell immune responses, providing a practical alternative to the systemic administration of IL12 for antitumor therapy.-
dc.language.isoen-
dc.titleHeterodimeric Fc-fused IL12 shows potent antitumor activity by generating memory CD8(+) T cells-
dc.typeArticle-
dc.identifier.pmid29900039-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993495/-
dc.subject.keywordImmunoglobulin heterodimeric Fc-
dc.subject.keywordInflammation and cancer-
dc.subject.keywordInterleukin 12-
dc.subject.keywordModels of immunostimulation-
dc.subject.keywordTherapeutic antibodies-
dc.subject.keywordanti-tumor therapy-
dc.subject.keywordlarge established immunogenic tumors-
dc.subject.keywordmemory CD8+ T cells-
dc.subject.keywordmonovalent binding format-
dc.contributor.affiliatedAuthor김, 철호-
dc.type.localJournal Papers-
dc.identifier.doi10.1080/2162402X.2018.1438800-
dc.citation.titleOncoimmunology-
dc.citation.volume7-
dc.citation.number7-
dc.citation.date2018-
dc.citation.startPagee1438800-
dc.citation.endPagee1438800-
dc.identifier.bibliographicCitationOncoimmunology, 7(7). : e1438800-e1438800, 2018-
dc.identifier.eissn2162-402X-
dc.relation.journalidJ021624011-
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Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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