Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma
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ORIGINAL ARTICLE
Anti‑human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma Nuchjira Takheaw1 · Gunya Sittithumcharee2 · Ryusho Kariya2 · Watchara Kasinrerk1,3 · Seiji Okada2 Received: 21 March 2020 / Accepted: 5 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords Mantle cell lymphoma · CD99 · Monoclonal antibody · Cancer immunotherapy · Cytotoxicity Abbreviations CCND1 Cyclin D1 CD Cluster of differentiation FITC Fluorescein isothiocyanate HRP Horseradish peroxidase PE Phycoerythrin
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02789-0) contains supplementary material, which is available to authorized users. * Watchara Kasinrerk [email protected] * Seiji Okada okadas@kumamoto‑u.ac.jp 1
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
2
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860‑0811, Japan
3
Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
Introduction CD99, also known as E2, is an extensive O-glycosylated type I single-chain transmembrane protein [1]. CD99 molecules express at different levels on several human cell types, both hematopoietic and non-hematopoietic [2–4]. These molecules display two isoforms; CD99 long form (wild-type) and alternative splicing CD99 short form (truncated) [5]. The expression of CD99 isoforms differs among cell types, and elicits distinct functions [6–8]. Multifunction of CD99 has been demonstrated in both physiological and pathological conditions [9]. It has been implicated in numerous cellular processes including cell apoptosis [10, 11]
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