Harnessing the Potential of NK Cell-Based Immunotherapies against Multiple Myeloma

Abstract

Natural killer (NK) cell-based therapies have emerged as promising anticancer treatments due to their potency as cytolytic effectors and synergy with concurrent treatments. Multiple myeloma (MM) is an aggressive B-cell malignancy that, despite development of novel therapeutic agents, remains incurable with a high rate of relapse. In MM, the inhospitable tumor microenvironment prevents host NK cells from exerting their cytolytic function. The development of NK cell immunotherapy works to overcome this altered immune landscape and can be classified in two major groups based on the origin of the cell: autologous or allogeneic. In this review, we compare the treatments in each group, such as autologous chimeric antigen receptor (CAR) NKs and allogeneic off-the-shelf NK cell infusions, and their combinatorial effect with existing MM therapies including monoclonal antibodies and proteasome inhibitors. We also discuss their placement in clinical treatment regimens based on the immune profile of each patient. Through this examination, we would like to discover precisely when each NK cell-based treatment will produce the maximum benefit to the MM patient.

Keywords: NK cells; allogeneic; autologous; daratumumab; isatuximab; multiple myeloma.

Figure 1

Schematic representation of the immunosuppressive MM microenvironment and the deleterious effect on NK cell anti-myeloma function. Created with BioRender.com.

Figure 2

Schematic representation of the main therapeutic protocols described in Section 4.2. Abbreviations are the same as used in Table 1 and Table 2.