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An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer
DC Field | Value | Language |
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dc.contributor.author | Huang, M | - |
dc.contributor.author | Park, J | - |
dc.contributor.author | Seo, J | - |
dc.contributor.author | Ko, S | - |
dc.contributor.author | Yang, YH | - |
dc.contributor.author | Lee, Y | - |
dc.contributor.author | Kim, HJ | - |
dc.contributor.author | Lee, BS | - |
dc.contributor.author | Lee, YS | - |
dc.contributor.author | Ko, BJ | - |
dc.contributor.author | Jung, ST | - |
dc.contributor.author | Park, D | - |
dc.contributor.author | Yoo, TH | - |
dc.contributor.author | Kim, CH | - |
dc.date.accessioned | 2024-09-10T06:21:40Z | - |
dc.date.available | 2024-09-10T06:21:40Z | - |
dc.date.issued | 2024 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/32735 | - |
dc.description.abstract | The 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.iso | en | - |
dc.subject.MESH | ADP Ribose Transferases | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antineoplastic Agents | - |
dc.subject.MESH | Apoptosis | - |
dc.subject.MESH | Bacterial Toxins | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Movement | - |
dc.subject.MESH | Cetuximab | - |
dc.subject.MESH | ErbB Receptors | - |
dc.subject.MESH | Exotoxins | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Head and Neck Neoplasms | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunoglobulin G | - |
dc.subject.MESH | Immunotoxins | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred BALB C | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Pseudomonas aeruginosa Exotoxin A | - |
dc.subject.MESH | Virulence Factors | - |
dc.subject.MESH | Xenograft Model Antitumor Assays | - |
dc.title | An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer | - |
dc.type | Article | - |
dc.identifier.pmid | 38949635 | - |
dc.subject.keyword | antibody-drug conjugate | - |
dc.subject.keyword | cetuximab | - |
dc.subject.keyword | epidermal growth factor receptor | - |
dc.subject.keyword | head and neck cancer | - |
dc.subject.keyword | immunotoxin | - |
dc.subject.keyword | peptide-directed photo-crosslinking | - |
dc.contributor.affiliatedAuthor | Lee, BS | - |
dc.contributor.affiliatedAuthor | Lee, YS | - |
dc.contributor.affiliatedAuthor | Kim, CH | - |
dc.type.local | Journal Papers | - |
dc.identifier.doi | 10.1096/fj.202301968R | - |
dc.citation.title | FASEB journal | - |
dc.citation.volume | 38 | - |
dc.citation.number | 13 | - |
dc.citation.date | 2024 | - |
dc.citation.startPage | e23759 | - |
dc.citation.endPage | e23759 | - |
dc.identifier.bibliographicCitation | FASEB journal, 38(13). : e23759-e23759, 2024 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.identifier.eissn | 1530-6860 | - |
dc.relation.journalid | J008926638 | - |
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