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

Cancer Immunol Immunother. 2021 Jun;70(6):1557-1567. doi: 10.1007/s00262-020-02789-0. Epub 2020 Nov 19.

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: CD99; Cancer immunotherapy; Cytotoxicity; Mantle cell lymphoma; Monoclonal antibody.

MeSH terms

  • 12E7 Antigen / antagonists & inhibitors
  • 12E7 Antigen / immunology
  • 12E7 Antigen / metabolism*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Proliferation
  • Complement Activation*
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / immunology
  • Lymphoma, Mantle-Cell / pathology
  • Lymphoma, Mantle-Cell / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • 12E7 Antigen
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CD99 protein, human