Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions

Abstract

Adoptive T Cell Therapy (ACT) is a kind of immunotherapy that eliminates target cells by autologous T cells. Since the mechanism of adoptive immune was elucidated, ACT has been developed for more than half a century. As one of ACTs, chimeric antigen receptor (CAR)-T cell therapy produced remarkable clinical responses in some hematological malignancies that is considered revolutionary strategy of immunotherapy. However, the effects of CAR-T cell therapy in solid tumors are hindered by immunosuppressive environment and limit of CAR to only recognize antigens on the cell surface. T cell receptor-engineered T cell (TCR-T) therapy is another type of ACT that the TCR is programmed to match crucial tumor antigens according to next-generation sequencing and bioinformatics analysis. The therapy overcomes the obstacles in solid tumor treatment by CAR-T, while there are also some problems dampening the response such as tumor immune escape, T cell exhaustion and toxicity. Beyond oncology, ACT is also applied in autoimmune diseases for it can specifically target and kill related immunocytes. In this review, we summarize the characteristics and clinical trials of CAR-T and TCR-T for cancer and autoimmune diseases. Differences, challenges and prospect of these ACTs are also described for reference to novel strategy of ACT.