CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer

SIMPLE SUMMARY: New approaches in adoptive immunotherapy using chimeric antigen receptor (CAR)-modified cells have been developing very quickly in recent years, entering into clinical trials and being accepted by health agencies worldwide. Although the classical CAR therapies using genetically engineered T cells (CAR-T) are quite effective in curing resistant and refractory blood disorders, they are less efficient in fighting solid tumors. Therefore, intense research is ongoing to modify the CAR constructs and to use different types of immune cells as platforms for CAR-based therapies in order to make them more efficient and safer. This review summarizes new approaches to CAR therapy, with a particular focus on recent achievements and the benefits of genetic engineering of NK cells. ABSTRACT: Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms. However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and neurotoxicity associated with CAR-T cell infusion, have raised some concerns about the broad application of this therapy. Natural killer (NK) cells have been identified as promising alternative platforms for CAR-based therapies because of their unique features, such as a lack of human leukocyte antigen (HLA)-matching restriction, superior safety, and better anti-tumor activity when compared with CAR-T cells. The lack of CRS, neurotoxicity, or GVHD, in the case of CAR-NK therapy, in addition to the possibility of using allogeneic NK cells as a CAR platform for “off-the-shelf” therapy, opens new windows for strategic opportunities. This review underlines recent design achievements in CAR constructs and summarizes preclinical studies’ results regarding CAR-NK therapies’ safety and anti-tumor potency. Additionally, new approaches in CAR-NK technology are briefly described, and currently registered clinical trials are listed.