Nanotechnology‐Based CAR‐T Strategies for Improving Efficacy and Safety of Tumor Immunotherapy

Abstract Therapeutic responses to chimeric antigen receptor (CAR) T cell therapy in patients with limited treatment options have been appealing in several clinical trials. However, the efficacy of CAR‐T therapy has been challenged by several obstacles when treating patients with solid tumors, such as severe toxicities, restricted access to tumor sites, suboptimal therapeutic persistence, and manufacturing issues. Nanotechnology has the advantages of protecting CAR‐T cells from being suppressed by tumor microenvironment (TME) and favorably adapting immune‐modulating drugs’ pharmacokinetics by modifying their spatiotemporal release profiles. Loaded with nanoparticles and packed onto CAR‐T cells, immune‐modulating drugs can be delivered to the tumor site and lymph node more efficiently, stimulating the expansion and activity of CAR‐T cells. To protect normal tissues from the nonspecific toxicity of the activated CAR‐T cells, formulations are optimized toward tumor targeting delivery of nanotechnology. This review summarizes the nanotechnology strategies to improve the safety and efficacy of CAR‐T therapy. In addition, the unsolved problems existing in the clinical application of CAR‐T therapy are focused on, where study and exploration by the way of nanotechnology is needed.