Natural killer cells may be scaled and engineered as a next generation, off-the-shelf cell therapy for cancer

The advent of immunotherapies for cancer, and more recently of cellular immunotherapies, has substantially altered the treatment landscape. In hematological malignancies, complete response rates to CAR-T cells can exceed 80%. These responses are often durable in nature and have attracted considerable excitement and investment in the development of cell therapies for an expanded range of indications, particularly in solid tumors. The continued progress of cell therapies depends on overcoming key obstacles that include a lengthy and costly manufacturing process, a high degree of product variability, risks of severe adverse events, and limited available targets. Natural killer (NK) cells have the potential to overcome these limitations. NK cells are highly potent lymphocytes that target cancer through multiple broadly expressed activating ligands; they can be used allogeneically without posing a risk of graft-versus-host disease (GvHD). In recent years, technologies have been developed that allow their efficient expansion and engineering. We will describe the current status of development of NK cell therapies as targeted, off-the-shelf, allogeneic cell therapies for cancer, highlighting the different approaches that have been taken for their effective exploitation, and will outline remaining obstacles to the advancement of the field.

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