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An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer

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dc.contributor.authorHuang, M-
dc.contributor.authorPark, J-
dc.contributor.authorSeo, J-
dc.contributor.authorKo, S-
dc.contributor.authorYang, YH-
dc.contributor.authorLee, Y-
dc.contributor.authorKim, HJ-
dc.contributor.authorLee, BS-
dc.contributor.authorLee, YS-
dc.contributor.authorKo, BJ-
dc.contributor.authorJung, ST-
dc.contributor.authorPark, D-
dc.contributor.authorYoo, TH-
dc.contributor.authorKim, CH-
dc.date.accessioned2024-09-10T06:21:40Z-
dc.date.available2024-09-10T06:21:40Z-
dc.date.issued2024-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/32735-
dc.description.abstractThe epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.-
dc.language.isoen-
dc.subject.MESHADP Ribose Transferases-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Agents-
dc.subject.MESHApoptosis-
dc.subject.MESHBacterial Toxins-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Movement-
dc.subject.MESHCetuximab-
dc.subject.MESHErbB Receptors-
dc.subject.MESHExotoxins-
dc.subject.MESHFemale-
dc.subject.MESHHead and Neck Neoplasms-
dc.subject.MESHHumans-
dc.subject.MESHImmunoglobulin G-
dc.subject.MESHImmunotoxins-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Nude-
dc.subject.MESHPseudomonas aeruginosa Exotoxin A-
dc.subject.MESHVirulence Factors-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleAn epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer-
dc.typeArticle-
dc.identifier.pmid38949635-
dc.subject.keywordantibody-drug conjugate-
dc.subject.keywordcetuximab-
dc.subject.keywordepidermal growth factor receptor-
dc.subject.keywordhead and neck cancer-
dc.subject.keywordimmunotoxin-
dc.subject.keywordpeptide-directed photo-crosslinking-
dc.contributor.affiliatedAuthorLee, BS-
dc.contributor.affiliatedAuthorLee, YS-
dc.contributor.affiliatedAuthorKim, CH-
dc.type.localJournal Papers-
dc.identifier.doi10.1096/fj.202301968R-
dc.citation.titleFASEB journal-
dc.citation.volume38-
dc.citation.number13-
dc.citation.date2024-
dc.citation.startPagee23759-
dc.citation.endPagee23759-
dc.identifier.bibliographicCitationFASEB journal, 38(13). : e23759-e23759, 2024-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1530-6860-
dc.relation.journalidJ008926638-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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