Int J Biol Sci 2022; 18(5):1974-1988. doi:10.7150/ijbs.68148 This issue

Review

Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies

Hao-Tian Wu1, Xiang-Yu Zhao1,2✉

1. Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, No. 11 South Street of Xizhimen, Xicheng District, Beijing 100044, China.
2. Collaborative Innovation Center of Hematology, China.

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Citation:
Wu HT, Zhao XY. Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies. Int J Biol Sci 2022; 18(5):1974-1988. doi:10.7150/ijbs.68148. Available from https://www.ijbs.com/v18p1974.htm

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Abstract

Graphic abstract

CD38 is highly expressed on multiple myeloma (MM) cells and plays a role in regulating tumor generation and development. CD38 monoclonal antibodies (mAbs) have been used as an effective therapy for MM treatment by various mechanisms, including complement-dependent cytotoxic effects, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, programmed cell death, enzymatic modulation, and immunomodulation. Although CD38 mAbs inhibit the proliferation and survival of MM cells, there are substantial side effects on antitumoral NK cells. The NK-mediated immune response needs to be further evaluated to minimize the adverse effects of NK cell loss. The killing effect of CD38 mAbs on CD38high NK cells should be minimized and the potential combination of CD38low/- NK cells and CD38 mAbs should be maximized to better benefit from their therapeutic efficacy against MM. CD38 mAb effects against MM can be maximized by combination therapies with immunomodulatory imide drugs (IMiDs), proteasome inhibitors (PIs), anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies, or cellular therapies for the treatment of MM, especially in patients with relapsed or refractory MM (R/R MM) and drug-resistant MM.

Keywords: multiple myeloma, CD38, monoclonal antibody, NK cells, combination therapy