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 outcomes 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 monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its beneficial effect, 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/off-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.

Automated summary

CAR T cell therapy has emerged as a promising treatment option for hematological malignancies, particularly B cell malignancies. However, its effectiveness in solid tumors is hindered by various complications, such as the immunosuppressive tumor microenvironment, tumor antigen heterogeneity, and limited accessibility to tumor cells. Strategies have been recommended to overcome these challenges and enhance the performance of infused T cells.