Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes.

The advent of modern synthetic-biology tools has enabled the development of cellular treatments with engineered specificity, leading to a new paradigm in anti-cancer immunotherapy. T cells have been at the forefront of such development, with six chimeric antigen receptor (CAR)-modified T cell products approved by the United States Food and Drug Administration for the treatment of hematological malignancies in the last five years. Natural killer (NK) cells are innate lymphocytes with potent cytotoxic activities, and they have become an increasingly attractive alternative to T cell therapies due to their potential for allogeneic, "off-the-shelf" applications. However, both T cells and NK cells face numerous challenges, including antigen escape, the immunosuppressive tumor microenvironment, and potential for severe toxicity. Many synthetic-biology strategies have been developed to address these obstacles, most commonly in the T-cell context. In this review, we discuss the array of strategies developed to date, their application in the NK-cell context, as well as opportunities and challenges for clinical translation.