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

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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.

Original languageEnglish (US)
Pages (from-to)346-352
Number of pages7
JournalJournal of Clinical Investigation
Volume117
Issue number2
DOIs
StatePublished - Feb 1 2007

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Anti-Idiotypic Antibodies
Carcinoma
Lung
Mutation
Neoplasms
Phosphotransferases
Therapeutics
Non-Small Cell Lung Carcinoma
Antibodies
epidermal growth factor receptor VIII
Epitopes
Squamous Cell Carcinoma
Lung Neoplasms
Monoclonal Antibodies
Apoptosis
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Li, D., Ji, H., Zaghlul, S., McNamara, K., Liang, M. C., Shimamura, T., ... Wong, K. K. (2007). Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas. Journal of Clinical Investigation, 117(2), 346-352. https://doi.org/10.1172/JCI30446

Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas. / Li, Danan; Ji, Hongbin; Zaghlul, Sara; McNamara, Kate; Liang, Mei Chih; Shimamura, Takeshi; Kubo, Shigeto; Takahashi, Masaya; Chirieac, Lucian R.; Padera, Robert F.; Scott, Andrew M.; Jungbluth, Achim A.; Cavenee, Webster K.; Old, Lloyd J.; Demetri, George D.; Wong, Kwok Kin.

In: Journal of Clinical Investigation, Vol. 117, No. 2, 01.02.2007, p. 346-352.

Research output: Contribution to journalArticle

Li, D, Ji, H, Zaghlul, S, McNamara, K, Liang, MC, Shimamura, T, Kubo, S, Takahashi, M, Chirieac, LR, Padera, RF, Scott, AM, Jungbluth, AA, Cavenee, WK, Old, LJ, Demetri, GD & Wong, KK 2007, 'Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas', Journal of Clinical Investigation, vol. 117, no. 2, pp. 346-352. https://doi.org/10.1172/JCI30446
Li, Danan ; Ji, Hongbin ; Zaghlul, Sara ; McNamara, Kate ; Liang, Mei Chih ; Shimamura, Takeshi ; Kubo, Shigeto ; Takahashi, Masaya ; Chirieac, Lucian R. ; Padera, Robert F. ; Scott, Andrew M. ; Jungbluth, Achim A. ; Cavenee, Webster K. ; Old, Lloyd J. ; Demetri, George D. ; Wong, Kwok Kin. / Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 2. pp. 346-352.
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