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Abstract
Chimeric antigen receptor (CAR) T cells are a rapidly emerging form of cancer treatment,
and have resulted in remarkable responses in refractory lymphoid malignancies. However,
their widespread clinical use is limited by toxicity related to cytokine release syndrome
and neurotoxicity, the logistic complexity of their manufacturing, cost and time-to-treatment
for autologous CAR-T cells, and the risk of graft-versus-host disease (GvHD) associated
with allogeneic CAR-T cells. Natural killer (NK) cells have emerged as a promising
source of cells for CAR-based therapies due to their ready availability and safety
profile. NK cells are part of the innate immune system, providing the first line of
defence against pathogens and cancer cells. They produce cytokines and mediate cytotoxicity
without the need for prior sensitisation and have the ability to interact with, and
activate other immune cells. NK cells for immunotherapy can be generated from multiple
sources, such as expanded autologous or allogeneic peripheral blood, umbilical cord
blood, haematopoietic stem cells, induced pluripotent stem cells, as well as cell
lines. Genetic engineering of NK cells to express a CAR has shown impressive preclinical
results and is currently being explored in multiple clinical trials. In the present
review, we discuss both the preclinical and clinical trial progress made in the field
of CAR NK-cell therapy, and the strategies to overcome the challenges encountered.