In vivo engineering chimeric antigen receptor immune cells with emerging nanotechnologies

Adoptive cell therapy with chimeric antigen receptor (CAR) has revolutionized cancer treatment in the past decade. Now several adoptive cell therapies are approved, and researchers are extending the application of adoptive cell therapy beyond oncology, such as autoimmune diseases, inherited blood disorders, infectious diseases and fibrosis. Evidence from clinical studies underscores the potential of cell therapy in cancer and noncancerous conditions. However, conventional manufacture of adoptive CAR-cell ex vivo is time-consuming and expensive in which immune cells are extracted from the patients, engineered to target cancer cells and reinjected to the body. The ways to produce CAR-cell in the body, as a promising alternative, may make the awfully expensive and personalized cell therapy more accessible. Here, we thoroughly summarize the current state of clinical trials on adoptive cell therapy, representing by CAR-T, CAR-nature killer cell (CAR-NK) and CAR-Macrophage (CAR-M), and highlight the latest advances in off-the-shelf nanocarrier- and virus-based in vivo CAR cargo delivery strategies, and corresponding precision targeting strategies, to provide a future perspective regarding in vivo engineering CAR-cell.