Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas

Danan Li, Hongbin Ji, Sara Zaghlul, Kate McNamara, Mei-Chih Liang, Takeshi Shimamura, Shigeto Kubo, Masaya Takahashi, Lucian R. Chirieac, Robert F. Padera, Andrew M. Scott, Achim A. Jungbluth, Webster K. Cavenee, Lloyd J. Old, George D. Demetri, Kwok Kin Wong*


研究成果: Article同行評審

45 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)346-352
期刊Journal of Clinical Investigation
出版狀態Published - 1 2月 2007


深入研究「Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas」主題。共同形成了獨特的指紋。