Chimeric antigen receptor T cell (CAR-T)
therapy is a late-model of immune
cell therapy that has been shown to be effective in refractory/recurrent
B-cell leukemia and
lymphoma. Compared with the traditional anti-
tumor methods, CAR-T cell therapy has the advantages of higher specificity, stronger lethality and longer-lasting efficacy. Although CAR-T cells have made significant progress in the treatment of
hematologic malignancies, diverse difficulties remain in the treatment of solid
tumors, including immune escape due to
tumor antigen heterogeneity, preventing entry or limiting the persistence of CAR-T cells by physical or
cytokine barriers and along with other immunosuppressive molecule and cells in the tumor microenvironment (TME). Otherwise, the intracellular signaling of CAR also impact on CAR-T cells persistence. Appropriate modification of intracellular costimulatory molecular signal in the structure of CAR or coexpression of CAR and
cytokines can provide a way to enhance CAR-T cells activity. Additionally, CAR-T cells dysfunction due to T cell exhaustion is associated with multi-factors, especially
transcription factors, such as c-Jun, NR4A. Engineering CAR-T cells to coexpress or knockout
transcription factors in favor of TCM memory CAR-T cells differentiation was proved to prolonged the survival of CAR-T cells. Finally, combination of CAR-T cells with oncolytic viruses, nanoparticles or
immune checkpoint inhibitors provides an effective measure to improve CAR-T cells function. Here, we discuss all of these advances and challenges and review promising strategies for treating solid
tumors. In particular, we also highlight that CAR-T cells have enormous potential to be used in combination with other
immunotherapies.