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 microenviron-ment, 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.

Automated summary

The development of modern synthetic-biology tools has revolutionized cellular treatments, particularly in anticancer immunotherapy. The FDA has approved six chimeric antigen receptor-modified T-cell products in the last 5 years, demonstrating the potential of engineered T cells in treating hematologic malignancies. Natural killer (NK) cells, with their potent cytotoxic activities and allogeneic capabilities, have emerged as an attractive alternative to T-cell therapies. However, both T cells and NK cells face challenges such as antigen escape, tumor microenvironment immunosuppression, and potential toxicity. Synthetic-biology strategies have been developed to address these obstacles, primarily in the T-cell context. This review explores the strategies, applications, and clinical translation opportunities and challenges for NK-cell therapies.