Anti-CD133 Monoclonal Antibody CMab-43 Exerts Antitumor Activity in a Mouse Xenograft Model of Colon Cancer
Anti-CD133 Monoclonal Antibody CMab-43 Exerts Antitumor Activity in a Mouse Xenograft Model of Colon Cancer
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抗 CD133 单克隆抗体 CMab-43 在小鼠结肠癌异种移植模型中发挥抗肿瘤活性
DOI：
10.1089/mab.2019.0002
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发表时间：
2019
影响因子：
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通讯作者：
Kaneko Mika K.
中科院分区：
文献类型：
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作者：
Kato Yukinari;Ohishi Tomokazu;Yamada Shinji;Itai Shunsuke;Furusawa Yoshikazu;Sano Masato;Nakamura Takuro;Kawada Manabu;Kaneko Mika K.
癌症干细胞有助于肿瘤发生、转移、复发和化学抗性。CD 133/CD 133 -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。在我们以前的研究中，我们开发了几种抗CD 133单克隆抗体，使用基于细胞的免疫和筛选（CBIS）方法，然后通过流式细胞术，蛋白质印迹和免疫组织化学分析表征其功效。100个克隆之一，CMab-43（IgG 2a，κ），表现出对结肠癌细胞的敏感和特异性反应。本研究旨在研究CMab-43的抗肿瘤活性。将Caco-2细胞（人结肠癌细胞系）皮下植入裸鼠的侧腹。将CMab-43和对照小鼠IgG注射到小鼠的腹膜腔中三次。在Caco-2异种移植模型的对照和CMab-43处理的小鼠中观察到肿瘤形成。在第12、14和17天，与对照小鼠IgG相比，CMab-43显著减少Caco-2异种移植物的肿瘤发展。我们的结果累积表明，CMab-43可用于针对表达CD 133的结肠癌的抗体治疗。
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 (IgG2a, 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.