CAR T-cell therapy has garnered significant excitement due to its success for hematological malignancies in clinical studies leading to the FDA approval of three CD19-targeted CAR T-cell products. In contrast, the clinical experience with CAR T-cell therapy for solid tumors and brain tumors has been less encouraging with only a few patients achieving complete responses. Clinical and preclinical studies have identified multiple ‘roadblocks’ including i) a limited array of targetable antigens and heterogenous antigen expression, ii) limited T-cell fitness and survival before reaching tumor sites, iii) inability of T cells to efficiently traffic to tumor sites and penetrate physical barriers, and iv) an immunosuppressive tumor microenvironment. Here researchers review these challenges and discuss strategies that investigators have taken to improve the effector function of CAR T cells for the adoptive immunotherapy of solid tumors.
The review appeared in September 16th online issue of Mol Ther (https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30472-X#%20)