Main Issues and Current Strategies in Enhancing the Efficacy of Chimeric Antigen Receptor T-Cell Therapy among Tumor Treatments

摘要

With the popularity of immunotherapy, the technology of chimeric antigen receptor (CAR) modified T cells has received widespread attention. To date, the most successful and prevalent use of CAR T cell therapy is the CAR T cells targeting CD19 in B cell malignancies, such as acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL), as well as B cell non-Hodgkin Lymphoma (NHL). Concerning the remarkable success, a great many clinical trials applying CAR T cell therapy to solid tumors have been carried out, but these results have shown disappointing results. Several reasons may contribute to the limited effectiveness of CAR therapy in solid tumor, such as antigens on solid cancers are often heterogenous, physical barriers constrain the infiltration of T cells, and the repeating targeting of CAR T cells may give selective pressure on tumors. In this paper, according to the screening of specific antigens, optimization of receptor structure, affinity of T cells binding tumor antigens and CAR T cells homing, the existing improvement direction and feasible optimization of CAR-T technology has been discussed. The safety considerations (correlated to toxicity) of CARs therapy, the time and money cost of CAR T cells manufacturing, the cryopreservation of CAR T cells, formulation general principles for quality assurance, if these aspects mentioned above are solved, CARs therapy in solid tumors will have great application prospects in clinical use.