Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts
| العنوان: | Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts |
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| المؤلفون: | Seung Won Choi, Do Hyun Nam, Hye Won Lee, Harim Koo, Eunju Son, Yejin Kim, Heekyoung Yang, Yangmi Lim, Minkyu Hur, Donggeon Kim, Kyoungmin Lee |
| المصدر: | Cancers Cancers, Vol 12, Iss 3210, p 3210 (2020) Volume 12 Issue 11 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.drug_class, Cell, monoclonal, amplification, Monoclonal antibody, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Growth factor receptor, In vivo, medicine, Epidermal growth factor receptor, xenograft, Cetuximab, biology, business.industry, glioblastoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Monoclonal, Cancer research, biology.protein, Biomarker (medicine), business, epidermal growth factor receptor, medicine.drug |
| الوصف: | 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&ndash 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c71fe31acd2bdcfee047aaaaa2e02a5a https://pubmed.ncbi.nlm.nih.gov/33142709 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c71fe31acd2bdcfee047aaaaa2e02a5a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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