As chimeric antigen receptor (CAR) T cells have displayed an unprecedented efficacy in the treatment of CD19-positive malignances, it is believed that this cell therapy will be a milestone in the history of mankind's conquering of cancer. However, there are some issues that restrict CAR T cells from reaching their optimal anti-tumor capacity, especially in the treatment of solid tumors. Inhibitory cytokines, immune checkpoint molecules, hypoxia and other adverse factors have been reported to be involved in this process. To obtain better efficacy in the treatment of leukemia and solid tumors, we need to continuously upgrade CAR T cell technology by incorporating novel functional elements into CAR T cells to overcome these restrictions. In this review, we summarize recent advances regarding this topic.
Keywords: CAR T cells; Chemotherapeutic drugs; Cytokines; Hypoxia; Immune checkpoint molecules; Kinase inhibitors; Tumor microenvironment.