CAR NK cell therapy in hematologic malignancies and solid tumors; obstacles and strategies to overcome the challenges

Adoptive cell treatment (ACT) utilizing chimeric antigen receptors (CAR) diverts the specificity of safe cells against a target-specific antigen and portrays exceptional potential for cancer treatment. While CAR T cell treatment has risen as a breakthrough with unprecedented results within the therapeutic procedures of human malignancies, different deficiencies including challenging and costly generation processes, strict patient qualification criteria, and undesirable toxicity have ruined its application. Unlike T cells, the application of natural killer (NK) cells has attracted consideration as a reasonable alternative owing to the major histocompatibility complex (MHC)-independency, shorter life expectancy, the potential to create an off-the-shelf immune product, and potent antitumor properties. In this article, we provide an updated review of the differences between CAR T and CAR NK cells, current enhancements in CAR NK design, the available sources for collecting NK cells, and strategies for the transduction step of the CARs to NK cells. Furthermore, we focus on the published and ongoing preclinical and clinical studies of CAR NK treatment strategies both in hematologic malignancies and solid tumors. We also discuss limitations and plausible solutions to improve the perseverance, function, safety, and efficacy of CAR NK cells with a special focus on solid tumors.