Natural Killer Cells as Add-on Therapy for Multiple Myeloma is Showing Promise in the Lab

Nina Shah, MD, Hematologist from the University of California, San Francisco, discusses preclinical data demonstrating that a subset of human natural killer (NK) cells that lack expression of FcεRIγ (g-NK cells) enhance the efficacy of monoclonal antibody treatment in multiple myeloma patients.

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of myeloma cells. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.
As Dr. Shah explains, g-NK cells are potentially what was previously known as “memory” NK cells as they work with the immune system to recognize viruses and bacteria. In a preclinical study led by Dr. Shah, the ability of g-NK cells to improve the efficacy of monoclonal antibody treatments (e.g., daratumumab or elotuzumab) in multiple myeloma was examined. Results from in vitro assays showed g-NK cells had six-fold higher anti-myeloma cell-killing activity compared with conventional NK cells when combined with daratumumab or elotuzumab.

Additionally, in a mouse model of multiple myeloma that investigated tumor regression, the combination of g-NK cells and daratumumab led to a 99.9% reduction in tumor burden compared with the combination of conventional NK cells and daratumumab. At Day 57 post-tumor inoculation, all 7 mice treated with the g-NK cells in combination with daratumumab were alive, and the myeloma tumor burden was eliminated in 5 of 7 mice.

In contrast, on Day 57, no mice treated with conventional NK cells and daratumumab were alive. Further, as the cancer was allowed to grow for two weeks post-inoculation until therapy was started, this preclinical study resulted in a cancer regression model as opposed to a cancer suppression model, as is often seen in other preclinical NK cell studies.

According to Dr. Shah, Indapta Therapeutics hopes to have a clinical trial testing g-NK cells as a multiple myeloma treatment in the next 6-12 months.