Title: Selection, expansion, and unique pretreatment of allogeneic human natural killer cells with anti-CD38 monoclonal antibody for efficient multiple myeloma treatment

Abstract

Following promising results in various clinical trials with chimeric antigen receptor T cells, cellular immunotherapy is emerging as a new pillar in cancer treatment. However, there are some drawbacks to this novel therapy, including off-tumor toxicity, cost, and tumor recurrence in heterogeneous tumors. To overcome these constraints, we take advantage of the unique anti-tumor properties of natural killer (NK) cells. Our study’s goal was to obtain a clinically relevant number of allogeneic NK cells derived from peripheral blood (median of 14,050 million cells from a single donor) to target a wide range of solid and liquid tumor types. Allogeneic NK cells were combined with the approved anti-cluster of differentiation 38 (CD-38) monoclonal antibody Daratumumab to achieve a synergistic therapeutic effect against incurable multiple myeloma. To avoid unwanted fratricide, the combination treatment was refined with CD16 polymorphism donor selection and uncomplicated novel in vitro pretreatment, increasing the in vitro specific lysis by more than 20% against the CD-38 positive multiple myeloma cell line. After time-lapse imaging of mice with subcutaneous human multiple myeloma xenografts, we discovered that combining selected and pretreated NK cells with Daratumumab resulted in tumor volumes that were 43-fold smaller than controls.