TY - JOUR
T1 - A novel anti-EGFR monoclonal antibody (EMab-17) exerts antitumor activity against oral squamous cell carcinomas via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity
AU - Takei, Junko
AU - Kaneko, Mika Kato
AU - Ohishi, Tomokazu
AU - Kawada, Manabu
AU - Harada, Hiroyuki
AU - Kato, Yukinari
N1 - Funding Information:
The authors would like thank Ms. Akiko Harakawa (Institute of Microbial Chemistry) for technical assistance during animal experiments. The authors would also like to acknowledge Ms. Miyuki Yanaka, Ms. Saori Handa, Ms. Kayo Hisamatsu and Mr. Takuro Nakamura (Tohoku University) for in vitro experiment technical assistance. The present study was supported by the Japanese Agency for Medical Research and Development (grant nos. JP19am0401013, JP19am0101078 and JP19ae0101028) andtheJapaneseSocietyforthePromotionofScienceGrantsin Aid for Scientific Research (KAKENHI; grant nos. 17K07299 and 19K07705).
Funding Information:
The present study was supported by the Japanese Agency for Medical Research and Development (grant nos. JP19am0401013, JP19am0101078 and JP19ae0101028) and the Japanese Society for the Promotion of Science Grants in Aid for Scientific Research (KAKENHI; grant nos. 17K07299 and 19K07705).
Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.
PY - 2020
Y1 - 2020
N2 - The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) familyofreceptortyrosinekinases;itisatransmembranereceptor involved in cell growth and differentiation. EGFR homodimers or heterodimers in combination with other HER members, such as HER2 and HER3, activate downstream signaling cascades in many types of cancer, including oral squamous cell carcinoma(OSCC).Thepresentstudyproducednovelanti-EGFR monoclonal antibodies (mAbs) possessing antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and investigated antitumor activity. Mice were immunized with an EGFR-overexpressed glioblastoma cell line, LN229 (LN229/EGFR), after which ELISA was performed using recombinant EGFR. mAbs were subsequently selected according to their efficacy for LN229/EGFR, as determined via flow cytometry. After determining the subclass of mAbs, the EMab-17 (IgG2a, kappa) clone exhibited ADCC and CDC activities against two OSCC cell lines, HSC-2 and SAS. Furthermore, EMab-17 exerted antitumor activities against mouse xenograft models using HSC-2 and SAS, indicating that EMab-17 may be used in an antibody-based therapy for EGFR-expressing OSCC.
AB - The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) familyofreceptortyrosinekinases;itisatransmembranereceptor involved in cell growth and differentiation. EGFR homodimers or heterodimers in combination with other HER members, such as HER2 and HER3, activate downstream signaling cascades in many types of cancer, including oral squamous cell carcinoma(OSCC).Thepresentstudyproducednovelanti-EGFR monoclonal antibodies (mAbs) possessing antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and investigated antitumor activity. Mice were immunized with an EGFR-overexpressed glioblastoma cell line, LN229 (LN229/EGFR), after which ELISA was performed using recombinant EGFR. mAbs were subsequently selected according to their efficacy for LN229/EGFR, as determined via flow cytometry. After determining the subclass of mAbs, the EMab-17 (IgG2a, kappa) clone exhibited ADCC and CDC activities against two OSCC cell lines, HSC-2 and SAS. Furthermore, EMab-17 exerted antitumor activities against mouse xenograft models using HSC-2 and SAS, indicating that EMab-17 may be used in an antibody-based therapy for EGFR-expressing OSCC.
KW - Antibody-dependent cellular cytotoxicity
KW - Complement-dependent cytotoxicity
KW - Epidermal growth factor receptor
KW - Monoclonal antibody
KW - Oral squamous cell carcinoma
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U2 - 10.3892/ol.2020.11384
DO - 10.3892/ol.2020.11384
M3 - Article
AN - SCOPUS:85081676444
SN - 1792-1074
VL - 19
SP - 2809
EP - 2816
JO - Oncology Letters
JF - Oncology Letters
IS - 4
ER -
