Takei Junko, Kaneko Mika Kato, Ohishi Tomokazu, Kawada Manabu, Harada Hiroyuki, Kato Yukinari
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Oncol Lett. 2020 Apr;19(4):2809-2816. doi: 10.3892/ol.2020.11384. Epub 2020 Feb 10.
The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases; it is a transmembrane receptor 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). The present study produced novel anti-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 (IgG, 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.
表皮生长因子受体（EGFR）是人类表皮生长因子受体（HER）家族受体酪氨酸激酶的成员之一；它是一种参与细胞生长和分化的跨膜受体。EGFR同型二聚体或与其他HER成员（如HER2和HER3）结合的异型二聚体，可激活包括口腔鳞状细胞癌（OSCC）在内的多种癌症的下游信号级联反应。本研究制备了具有抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）的新型抗EGFR单克隆抗体（mAb），并研究了其抗肿瘤活性。用EGFR过表达的胶质母细胞瘤细胞系LN229（LN229/EGFR）免疫小鼠，之后使用重组EGFR进行酶联免疫吸附测定（ELISA）。随后根据通过流式细胞术测定的mAb对LN229/EGFR的效力来选择mAb。在确定mAb的亚类后，EMab-17（IgG，κ）克隆对两种OSCC细胞系HSC-2和SAS表现出ADCC和CDC活性。此外，EMab-17对使用HSC-2和SAS的小鼠异种移植模型具有抗肿瘤活性，这表明EMab-17可用于基于抗体的EGFR表达型OSCC治疗。
