Gene Transduction of Natural Killer Cells for Clinical Application

Autologous T cells expressing chimeric antigen receptor (CAR) have produced a spectacular response in hematological malignancies. This success of cellular therapy has inspired the exploration of the therapeutic potential of other immune cell types. In this regard, natural killer (NK) cells hold great potential as they can identify tumor cells by mechanisms that are different from those used by T cells and have a high cytotoxic capacity. Their capacity to recognize tumors and killing potency can be further enhanced by genetic modification. Our laboratory has developed a clinically adaptable method to manufacture genetically modified NK cells using retroviral vectors in compliance with current good manufacturing practice regulations. Here, we describe relevant technical procedures, including isolation of peripheral blood mononucleated cells from a leukapheresis product, T-cell depletion, stimulation and transduction of NK cells, and preparation of transduced NK cells for infusion.