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Article

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

1
Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation and 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan
2
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
3
New Industry Creation Hatchery Center, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
4
Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6037; https://doi.org/10.3390/ijms21176037
Received: 1 June 2020 / Revised: 12 August 2020 / Accepted: 20 August 2020 / Published: 21 August 2020
(This article belongs to the Section Molecular Oncology)
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. View Full-Text
Keywords: colorectal cancer; metastasis; epidermal growth factor receptor; antibody-dependent cell cytotoxicity; complement-dependent cytotoxicity colorectal cancer; metastasis; epidermal growth factor receptor; antibody-dependent cell cytotoxicity; complement-dependent cytotoxicity
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MDPI and ACS Style

Ohishi, T.; Kato, Y.; Kaneko, M.K.; Ohba, S.-i.; Inoue, H.; Harakawa, A.; Kawada, M. Anti-Metastatic Activity of an Anti-EGFR Monoclonal Antibody against Metastatic Colorectal Cancer with KRAS p.G13D Mutation. Int. J. Mol. Sci. 2020, 21, 6037. https://doi.org/10.3390/ijms21176037

AMA Style

Ohishi T, Kato Y, Kaneko MK, Ohba S-i, Inoue H, Harakawa A, Kawada M. Anti-Metastatic Activity of an Anti-EGFR Monoclonal Antibody against Metastatic Colorectal Cancer with KRAS p.G13D Mutation. International Journal of Molecular Sciences. 2020; 21(17):6037. https://doi.org/10.3390/ijms21176037

Chicago/Turabian Style

Ohishi, Tomokazu, Yukinari Kato, Mika K. Kaneko, Shun-ichi Ohba, Hiroyuki Inoue, Akiko Harakawa, and Manabu Kawada. 2020. "Anti-Metastatic Activity of an Anti-EGFR Monoclonal Antibody against Metastatic Colorectal Cancer with KRAS p.G13D Mutation" International Journal of Molecular Sciences 21, no. 17: 6037. https://doi.org/10.3390/ijms21176037

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