The Race of CAR Therapies: CAR-NK Cells for Fighting B-Cell Hematological Cancers

SIMPLE SUMMARY: Over the last few years, CAR-T cells have arisen as one of the most promising immunotherapies against relapsed or refractory hematological cancers. Despite their good results in clinical trials, there are some limitations to overcome, such as undesirable side-effects or the restraints of an autologous treatment. Therefore, CAR-NK cells have emerged as a good alternative for these kinds of treatments. This review discusses the advantages of CAR-NK cells compared to CAR-T cells, as well as the different sources and strategies in order to obtain these CAR-NK cells. ABSTRACT: Acute lymphoblastic leukemia (ALL) and Chronic lymphocytic leukemia (CLL) are the most common leukemias in children and elderly people, respectively. Standard therapies, such as chemotherapy, are only effective in 40% of ALL adult patients with a five-year survival rate and therefore new alternatives need to be used, such as immunotherapy targeting specific receptors of malignant cells. Among all the options, CAR (Chimeric antigen receptor)-based therapy has arisen as a new opportunity for refractory or relapsed hematological cancer patients. CARs were designed to be used along with T lymphocytes, creating CAR-T cells, but they are presenting such encouraging results that they are already in use as drugs. Nonetheless, their side-effects and the fact that it is not possible to infuse an allogenic CAR-T product without causing graft-versus-host-disease, have meant using a different cell source to solve these problems, such as Natural Killer (NK) cells. Although CAR-based treatment is a high-speed race led by CAR-T cells, CAR-NK cells are slowly (but surely) consolidating their position; their demonstrated efficacy and the lack of undesirable side-effects is opening a new door for CAR-based treatments. CAR-NKs are now in the field to stay.