Therapeutic Anti-egfr Antibody 806 Generates Responses in Murine De Novo Egfr Mutant-dependent Lung Carcinomas.
From: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
The Journal of clinical investigation
- Publish Date: Feb 2007
- ISSN: 0021-9738
- Volume: 117
- Issue: 2
- Pages: 346-52
- Medium: Print
- Language: English
- Citation (JAMA): Li Danan, Ji Hongbin, Zaghlul Sara, et al. Therapeutic Anti-egfr Antibody 806 Generates Responses in Murine De Novo Egfr Mutant-dependent Lung Carcinomas.. J. Clin. Invest. Feb 2007;117:346-52
Abstract
Activating EGFR mutations occur in human non-small cell lung cancer (NSCLC), with 5% of human lung squamous cell carcinomas having EGFRvIII mutations and approximately 10%-30% of lung adenocarcinomas having EGFR kinase domain mutations. An EGFR-targeting monoclonal antibody, mAb806, recognizes a conformational epitope of WT EGFR as well as the truncated EGFRvIII mutant. To explore the anticancer spectrum of this antibody for EGFR targeted cancer therapy, mAb806 was used to treat genetically engineered mice with lung tumors that were driven by either EGFRvIII or EGFR kinase domain mutations. Our results demonstrate that mAb806 is remarkably effective in blocking EGFRvIII signaling and inducing tumor cell apoptosis, resulting in dramatic tumor regression in the EGFRvIII-driven murine lung cancers. Another EGFR-targeting antibody, cetuximab, failed to show activity in these lung tumors. Furthermore, treatment of murine lung tumors driven by the EGFR kinase domain mutation with mAb806 also induced significant tumor regression, albeit to a less degree than that observed in EGFRvIII-driven tumors. Taken together, these data support the hypothesis that mAb806 may lead to significant advancements in the treatment of the population of NSCLC patients with these 2 classes of EGFR mutations.
Mesh Headings (Keywords): Animals, Antibodies, Monoclonal, Apoptosis, Cyclin-Dependent Kinase Inhibitor p16, Humans, Lung Neoplasms, Mice, Mice, Knockout, Mice, Mutant Strains, Mice, Transgenic, Mutation, Neoplasms, Hormone-Dependent, Phosphorylation, Receptor, Epidermal Growth Factor
Check for Full Text / PubMed Unique Identifier (PMID): 17256054
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.