Anti-metastatic activity of an anti-egfr monoclonal antibody against metastatic colorectal cancer with kras p.G13d mutation

Tomokazu Ohishi, Yukinari Kato, Mika K. Kaneko, Shun Ichi Ohba, Hiroyuki Inoue, Akiko Harakawa, Manabu Kawada

Research output: Contribution to journalArticlepeer-review

Abstract

The now clinically-used anti-epidermal growth factor receptor (EGFR) monoclonal antibodies have demonstrated significant efficacy only in patients with metastatic colorectal cancer (mCRC), with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS). However, no effective treatments for patients with mCRC with KRAS mutated tumors have been approved yet. Therefore, a new strategy for targeting mCRC with KRAS mutated tumors is desired. In the present study, we examined the anti-tumor activities of a novel anti-EGFR monoclonal antibody, EMab-17 (mouse IgG2a, kappa), in colorectal cancer (CRC) cells with the KRAS p.G13D mutation. This antibody recognized endogenous EGRF in CRC cells with or without KRAS mutations, and showed a high sensitivity for CRC cells in flow cytometry, indicating that EMab-17 possesses a high binding affinity to the endogenous EGFR. In vitro experiments showed that EMab-17 exhibited antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activities against CRC cells. In vivo analysis revealed that EMab-17 inhibited the metastases of HCT-15 and HCT-116 cells in the livers of nude mouse metastatic models, unlike the anti-EGFR monoclonal antibody EMab-51 of subtype mouse IgG1. In conclusion, EMab-17 may be useful in an antibody-based therapy against mCRC with the KRAS p.G13D mutation.

Original languageEnglish
Article number6037
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number17
DOIs
Publication statusPublished - 2020 Sep 1

Keywords

  • Antibody-dependent cell cytotoxicity
  • Colorectal cancer
  • Complement-dependent cytotoxicity
  • Epidermal growth factor receptor
  • Metastasis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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