Functional Chimeric Antigen Receptor-Expressing Natural Killer Cells Derived From Human Pluripotent Stem Cells

Natural killer (NK) cells are a key part in the innate immune system and have the ability to recognize diverse types of tumors and virally-infected targets. NK cells represent an attractive cell population for adoptive immunotherapy due to their ability to kill target cells in a human leukocyte antigen (HLA) non-restricted manner and without prior sensitization. Clinical studies using IL-2 activated NK cells demonstrate significant anti-tumor effects when adoptively transferred into patients with refractory leukemia (mainly AML). However, there has been a more limited response observed in clinical trials for the treatment of ovarian cancer and other solid malignancies. Chimeric antigen receptors (CARs) consist of an antigen-specific single chain antibody variable fragment fused to intracellular signaling domains derived from receptors involved in lymphocyte activation. CARs targeting various tumor-associated antigens have been developed and tested via expression in primary T cells with promising clinical results. However, engineering these T cells must be done on a patient-specific basis, thus limiting the number of patients who can be treated.