Hurdles to breakthrough in CAR T cell therapy of solid tumors

Autologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising out- comes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells. Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of mono- clonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its benefcial efect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/of-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the efectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.