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 anticancer immunotherapy. T cells have been at the forefront of such development, with six chimeric antigen receptor-modified T-cell products approved by the FDA for the treatment of hematologic malignancies in the last 5 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.

Engineering CAR-T Cells for Next-Generation Cancer Therapy.

T cells engineered to express chimeric antigen receptors (CARs) with tumor specificity have shown remarkable success in treating patients with hematologic malignancies and revitalized the field of adoptive cell therapy. However, realizing broader therapeutic applications of CAR-T cells necessitates engineering approaches on multiple levels to enhance efficacy and safety. Particularly, solid tumors present unique challenges due to the biological complexity of the solid-tumor microenvironment (TME). In this review, we highlight recent strategies to improve CAR-T cell therapy by engineering (1) the CAR protein, (2) T cells, and (3) the interaction between T cells and other components in the TME.