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Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts

Authors
 Kyoungmin Lee  ;  Harim Koo  ;  Yejin Kim  ;  Donggeon Kim  ;  Eunju Son  ;  Heekyoung Yang  ;  Yangmi Lim  ;  Minkyu Hur  ;  Hye Won Lee  ;  Seung Won Choi  ;  Do-Hyun Nam 
Citation
 CANCERS, Vol.12(11) : 3210, 2020-10 
Journal Title
CANCERS
Issue Date
2020-10
Keywords
amplification ; epidermal growth factor receptor ; glioblastoma ; monoclonal ; xenograft
Abstract
We aimed to evaluate the preclinical efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), against glioblastoma (GBM) tumors using patient-derived xenograft (PDX) models. A total of 15 distinct GBM PDX models were used to evaluate the therapeutic efficacy of GC1118. Genomic data derived from PDX models were analyzed to identify potential biomarkers associated with the anti-tumor efficacy of GC1118. A patient-derived cell-based high-throughput drug screening assay was performed to further validate the efficacy of GC1118. Compared to cetuximab, GC1118 exerted comparable growth inhibitory effects on the GBM tumors in the PDX models. We confirmed that GC1118 accumulated within the tumor by crossing the blood-brain barrier in in vivo specimens and observed the survival benefit in GC1118-treated intracranial models. Genomic analysis revealed high EGFR amplification as a potent biomarker for predicting the therapeutic efficacy of GC1118 in GBM tumors. In summary, GC1118 exerted a potent anti-tumor effect on GBM tumors in PDX models, and its therapeutic efficacy was especially pronounced in the tumors with high EGFR amplification. Our study supports the importance of patient stratification based on EGFR copy number variation in clinical trials for GBM. The superiority of GC1118 over other EGFR mAbs in GBM tumors should be assessed in future studies
Files in This Item:
T202005038.pdf Download
DOI
10.3390/cancers12113210
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Hospital Medicine (입원의학과) > 1. Journal Papers
Yonsei Authors
Lee, Hye Won(이혜원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191139
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