Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humH2Mab-250 in Human Breast Cancer Xenografts

被引:0
|
作者
Kaneko, Mika K. [1 ]
Suzuki, Hiroyuki [1 ]
Ohishi, Tomokazu [2 ,3 ]
Nakamura, Takuro [1 ]
Yanaka, Miyuki [1 ]
Tanaka, Tomohiro [1 ]
Kato, Yukinari [1 ]
机构
[1] Tohoku Univ, Dept Antibody Drug Dev, Grad Sch Med, 2-1 Seiryo Machi,Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Microbial Chem Res Fdn, Inst Microbial Chem BIKAKEN, 18-24 Miyamoto, Numazu, Shizuoka 4100301, Japan
[3] Microbial Chem Res Fdn, Inst Microbial Chem BIKAKEN, Lab Oncol, 3-14-23 Kamiosaki,Shinagawa Ku, Tokyo 1410021, Japan
基金
日本学术振兴会;
关键词
cancer-specific monoclonal antibody; HER2; ADCC; CDC; xenograft; breast cancer; COMPLEMENT; HER2; RITUXIMAB; OFATUMUMAB; RECEPTOR; CELLS; ERBB2;
D O I
10.3390/ijms26031079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial to develop cancer-specific mAbs (CasMabs) that can bind to cancer-specific antigens and exhibit antitumor activity in vivo, thereby reducing the risk of adverse effects. We previously screened mAbs targeting human epidermal growth factor receptor 2 (HER2) and successfully developed a cancer-specific anti-HER2 mAb, H2Mab-250/H2CasMab-2 (mouse IgG1, kappa). In this study, we assessed both the in vitro and in vivo antitumor efficacy of the humanized H2Mab-250 (humH2Mab-250). Although humH2Mab-250 showed lower reactivity to HER2-overexpressed Chinese hamster ovary-K1 (CHO/HER2) and breast cancer cell lines (BT-474 and SK-BR-3) than trastuzumab in flow cytometry, both humH2Mab-250 and trastuzumab showed similar antibody-dependent cellular cytotoxicity (ADCC) against CHO/HER2 and the breast cancer cell lines in the presence of effector splenocytes. In addition, humH2Mab-250 exhibited significant complement-dependent cellular cytotoxicity (CDC) in CHO/HER2 and the breast cancer cell lines compared to trastuzumab. Furthermore, humH2Mab-250 possesses compatible in vivo antitumor effects against CHO/HER2 and breast cancer xenografts with trastuzumab. These findings highlight the distinct roles of ADCC and CDC in the antitumor effects of humH2Mab-250 and trastuzumab and suggest a potential direction for the clinical development of humH2Mab-250 for HER2-positive tumors.
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页数:14
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