Bailey and Maus discuss current and potential synthetic biology and gene editing strategies (e.g. viral vectors, transposons, CRISPR, TALEN) for the development of immune cell-based therapies. Keeping in mind the dual goals of highly personalized and tumor-specific therapies and highly scalable and mass-produced treatment, T cells can be redesigned to improve targeting breadth and specificity, to reduce the impact of immunosuppressive molecules, and to directly modify the TME; similar capabilities can be employed with other immune cells (NK cells, macrophages, and stem cells). Applications in infectious and autoimmune diseases are briefly reviewed.
Autologous T cells that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the B cell antigen CD19 have yielded remarkable clinical responses in patients with B cell malignancies, and are now on the market as anticancer 'drugs'. Riding on this success, the field of immune cell engineering is rapidly growing, with creative solutions to major outstanding challenges, such as limitations in target antigen selection, the hostility of the tumor microenvironment and the logistical challenges of generating autologous therapies. Innovations in antigen receptor design, coupled with advances in gene transfer and gene-editing technologies, have enabled the engineering of T cells to have sophisticated sensing circuits, to have synthetic functionalities, and to be used as off-the-shelf, universal cellular products. As these technologies are applied to other immune cells, such as natural killer cells, hematopoietic cells or induced pluripotent stem cells, the potential to transform the treatment of many cancers, as well as other diseases, is palpably exciting. We discuss the pipeline of several influential innovations in the preclinical setting, the early translational results from clinical trials of these next-generation approaches, and the outlook for gene-modified or gene-edited cell therapies.
Author Info: (1) Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Cellular Immunotherapy Program, Can
Author Info: (1) Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, MA, USA. mvmaus@mgh.harvard.edu. Harvard Medical School, Boston, MA, USA. mvmaus@mgh.harvard.edu.
