Next Article in Journal
Lipopolysaccharide-Linked Enterobacterial Common Antigen (ECALPS) Occurs in Rough Strains of Escherichia coli R1, R2, and R4
Previous Article in Journal
Transcriptomic Analysis of Short-Term Salt Stress Response in Watermelon Seedlings
Open AccessArticle

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
Show Figures

Figure 1

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop