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

Authors
Huang, M | Park, J | Seo, J | Ko, S | Yang, YH | Lee, Y | Kim, HJ | Lee, BS  | Lee, YS  | Ko, BJ | Jung, ST | Park, D | Yoo, TH | Kim, CH
Citation
FASEB journal, 38(13). : e23759-e23759, 2024
Journal Title
FASEB journal
ISSN
0892-66381530-6860
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.
Keywords

MeSH

DOI
10.1096/fj.202301968R
PMID
38949635
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Ajou Authors
김, 철호  |  이, 복순  |  이, 윤상
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