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Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma

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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.

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Abbreviations

CCND1:

Cyclin D1

CD:

Cluster of differentiation

FITC:

Fluorescein isothiocyanate

HRP:

Horseradish peroxidase

PE:

Phycoerythrin

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Funding

This work was supported by the Distinguished Research Professor Grant (NRCT808/2563) of the National Research Council of Thailand, Chiang Mai University Center of Excellence Project and Japan Student Services Organization (JASSO) scholarship (Grant no. UTB1717401001).

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Authors and Affiliations

  1. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand

    Nuchjira Takheaw & Watchara Kasinrerk

  2. Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860-0811, Japan

    Gunya Sittithumcharee, Ryusho Kariya & Seiji Okada

  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

    Watchara Kasinrerk

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  1. Nuchjira Takheaw
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  4. Watchara Kasinrerk
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  5. Seiji Okada
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Contributions

NT conceived the study, designed and carried out experiments, analyzed data and drafted the manuscript. GS performed ADCC assay of IL-2 activated splenocytes and participated in in vivo experiments. RK participated in in vivo experiments. WK and SO conceived the study, and were involved in the experimental design, interpretation of results and editing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Watchara Kasinrerk or Seiji Okada.

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Mice were bred and cared for in the animal research facility according to institutional guidelines. All experimental procedures in this study were approved by the Institutional Animal Care and Use Committee at Kumamoto University, Japan.

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Takheaw, N., Sittithumcharee, G., Kariya, R. et al. Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma. Cancer Immunol Immunother 70, 1557–1567 (2021). https://doi.org/10.1007/s00262-020-02789-0

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