Nanotechnology Promotes Genetic and Functional Modifications of Therapeutic T Cells Against Cancer
Ahmed M. E. Abdalla, Lin Xiao, Miao Yu, Lixia Huang, Gendeal M. Fadlallah, Mario Gauthier, Chenxi Ouyang, Guang Yang
Abstract
Growing experience with engineered chimeric antigen receptor (CAR)-T cells has revealed some of the challenges associated with developing patient-specific therapy. The promising clinical results obtained with CAR-T therapy nevertheless demonstrate the urgency of advancements to promote and expand its uses. There is indeed a need to devise novel methods to generate potent CARs, and to confer them and track their anti-tumor efficacy in CAR-T therapy. A potentially effective approach to improve the efficacy of CAR-T cell therapy would be to exploit the benefits of nanotechnology. This report highlights the current limitations of CAR-T immunotherapy and pinpoints potential opportunities and tremendous advantages of using nanotechnology to 1) introduce CAR transgene cassettes into primary T cells, 2) stimulate T cell expansion and persistence, 3) improve T cell trafficking, 4) stimulate the intrinsic T cell activity, 5) reprogram the immunosuppressive cellular and vascular microenvironments, and 6) monitor the therapeutic efficacy of CAR-T cell therapy. Therefore, genetic and functional modifications promoted by nanotechnology enable the generation of robust CAR-T cell therapy and offer precision treatments against cancer.