抗人 CD99 抗体在套细胞淋巴瘤中发挥强大的抗肿瘤作用。
Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma.
机构信息
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860-0811, Japan.
出版信息
Cancer Immunol Immunother. 2021 Jun;70(6):1557-1567. doi: 10.1007/s00262-020-02789-0. Epub 2020 Nov 19.
CD99 is a surface molecule expressed on various cell types including cancer cells. Expression of CD99 on multiple myeloma is associated with CCND1-IGH fusion/t(11;14). This translocation has been reported to be a genetic hallmark of mantle cell lymphoma (MCL). MCL is characterized by overexpression of cyclin D1 and high tumor proliferation. In this study, high expression of CD99 on MCL cell lines was confirmed. Our generated anti-CD99 monoclonal antibody (mAb), termed MT99/3, exerted potent antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities against mantle B-cell lymphoma without direct cytotoxic effects. The anti-tumor activities of mAb MT99/3 were more effective in MCL than in other B-cell lymphomas. Moreover, in a mouse xenograft model using Z138 MCL cell line, treatment of mAb MT99/3 reduced tumor development and growth. Our study indicated that mAb MT99/3 is a promising immunotherapeutic candidate for mantle cell lymphoma therapy.
CD99 是一种在多种细胞类型上表达的表面分子，包括癌细胞。多发性骨髓瘤中 CD99 的表达与 CCND1-IGH 融合/ t(11;14)有关。该易位已被报道为套细胞淋巴瘤（MCL）的遗传标志。MCL 的特征是 cyclin D1 的过度表达和高肿瘤增殖。在这项研究中，证实了 MCL 细胞系上 CD99 的高表达。我们生成的抗 CD99 单克隆抗体（mAb），称为 MT99/3，对套细胞 B 细胞淋巴瘤具有强大的抗体依赖性细胞介导的细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）活性，而没有直接的细胞毒性作用。mAb MT99/3 的抗肿瘤活性在 MCL 中比在其他 B 细胞淋巴瘤中更有效。此外，在使用 Z138 MCL 细胞系的小鼠异种移植模型中，mAb MT99/3 的治疗减少了肿瘤的发展和生长。我们的研究表明，mAb MT99/3 是治疗套细胞淋巴瘤的一种很有前途的免疫治疗候选药物。
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