Kato Yukinari, Ohishi Tomokazu, Yamada Shinji, Itai Shunsuke, Furusawa Yoshikazu, Sano Masato, Nakamura Takuro, Kawada Manabu, Kaneko Mika K
1 Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
2 New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.
Monoclon Antib Immunodiagn Immunother. 2019 Apr;38(2):75-78. doi: 10.1089/mab.2019.0002. Epub 2019 Apr 10.
Cancer stem cells contribute to tumorigenesis, metastasis, recurrence, and chemoresistance. CD133/prominin-1-a pentaspan membrane glycoprotein-has been used as a stem cell biomarker for the isolation of stem-like cells from a variety of normal and pathological tissues. In our previous studies, we developed several anti-CD133 monoclonal antibodies using Cell-Based Immunization and Screening (CBIS) methods, followed by characterization of their efficacy by flow cytometry, western blotting, and immunohistochemical analyses. One of the 100 clones, CMab-43 (IgG, kappa), demonstrated a sensitive and specific reaction against colon cancer cells. This study aimed to investigate the antitumor activity of CMab-43. Caco-2 cells (human colon cancer cell line) were subcutaneously implanted into the flanks of nude mice. CMab-43 and control mouse IgG were injected three times into the peritoneal cavity of mice. Tumor formation was observed in the control and CMab-43-treated mice of Caco-2 xenograft models. CMab-43 significantly reduced tumor development of Caco-2 xenograft in comparison with the control mouse IgG on days 12, 14, and 17. Our results cumulatively suggest that CMab-43 is useful for antibody therapy against CD133-expressing colon cancers.
癌症干细胞促进肿瘤发生、转移、复发及化疗耐药。CD133/促红细胞膜蛋白-1（一种五跨膜糖蛋白）已被用作干细胞生物标志物，用于从多种正常和病理组织中分离干细胞样细胞。在我们之前的研究中，我们使用基于细胞的免疫和筛选（CBIS）方法开发了几种抗CD133单克隆抗体，随后通过流式细胞术、蛋白质印迹法和免疫组织化学分析对其疗效进行了表征。100个克隆中的一个，即CMab-43（IgG，κ），对结肠癌细胞表现出灵敏且特异的反应。本研究旨在探究CMab-43的抗肿瘤活性。将Caco-2细胞（人结肠癌细胞系）皮下植入裸鼠侧腹。将CMab-43和对照小鼠IgG注入小鼠腹腔3次。在Caco-2异种移植模型的对照小鼠和经CMab-43处理的小鼠中均观察到肿瘤形成。在第12、14和17天，与对照小鼠IgG相比，CMab-43显著降低了Caco-2异种移植瘤的生长。我们的结果累积表明，CMab-43可用于针对表达CD133的结肠癌的抗体治疗。
