Anti-Metastatic Activity of an Anti-EGFR Monoclonal Antibody against Metastatic Colorectal Cancer with <i>KRAS</i> p.G13D Mutation

• Main Authors: Tomokazu Ohishi, Yukinari Kato, Mika K. Kaneko, Shun-ichi Ohba, Hiroyuki Inoue, Akiko Harakawa, Manabu Kawada
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: International Journal of Molecular Sciences
• Subjects: colorectal cancer; metastasis; epidermal growth factor receptor; antibody-dependent cell cytotoxicity; complement-dependent cytotoxicity
• Online Access: https://www.mdpi.com/1422-0067/21/17/6037
• ISSN: 1661-6596; 1422-0067

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 (<i>KRAS</i>). However, no effective treatments for patients with mCRC with <i>KRAS</i> mutated tumors have been approved yet. Therefore, a new strategy for targeting mCRC with <i>KRAS</i> mutated tumors is desired. In the present study, we examined the anti-tumor activities of a novel anti-EGFR monoclonal antibody, EMab-17 (mouse IgG_2a, kappa), in colorectal cancer (CRC) cells with the <i>KRAS</i> p.G13D mutation. This antibody recognized endogenous EGRF in CRC cells with or without <i>KRAS</i> 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 <i>KRAS</i> p.G13D mutation.