CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization

Natural killer (NK) cells are specialized components of the innate immune system with an essential role in immune surveillance against multiple myeloma (MM). However, patients with MM often exhibit significant impairments in both the quantity and functionality of NK cells, particularly those who are refractory or have relapsed disease. Increasing evidence suggests that harnessing NK cells may provide a promising "off-the-shelf" therapeutic strategy for treating MM. Recent advancements in chimeric antigen receptor (CAR) engineering have enhanced the capabilities of NK cells, allowing them to target MM-associated antigens effectively. This innovative approach may help mitigate the off-target toxicities often associated with NK cells and address challenges such as the ability of MM cells to evade immune detection. CAR-NK therapy shows promise for B-cell malignancies, but its efficacy in MM has been less examined. This comprehensive review revealed that CAR-NK cells elicit a robust immune response against myeloma cells in preclinical studies conducted both in vitro and in vivo. Furthermore, the development of dual-CAR NK cell therapies indicates promise in overcoming myeloma escape mechanisms. Numerous clinical trials are currently underway to evaluate the efficacy and safety of CAR-NK cell therapy for individuals diagnosed with MM.