Advances and challenges of chimeric antigen receptor T cell therapy for solid tumors

Abstract

In recent years, cancer immunotherapy has attracted considerable attention in the field of biotherapy for the development of chimeric antigen receptor T (CAR-T) cell. CAR-T cells are capable of recognizing tumor cell surface antigens leading to kill tumor cells. Anti-CD19 CAR-T has achieved remarkable success in the treatment of hematopoietic malignancies. Whether it can benefit solid tumor patients to the same extent still faces great challenges, and it has been a focus of attention in immunotherapy for tumors.Compared with hematological malignancies, the microenvironment of solid tumor is more complex, and the screening of tumor specific antigen is more difficult. The infiltration of CAR-T cells from the blood system to the tumor site needs to overcome the tumor stromal barrier. Although part of CAR-T cells can infiltrate into tumor site, its function may be quickly inhibited by multiple factors in microenvironment. In this paper, authors discussed the challenges that CAR-T is facing for solid tumor treatment, including the specificity of the tumor antigen, the heterogeneity of the solid tumor antigen and the inhibitory effect of the tumor microenvironment, and proposed potential strategies to possibly overcome these hurdles. Authors believe that with the development of biotechnology, it will provide more abundant technical means to optimize the structure and function of CAR-T, and CAR-T will make breakthrough progress in the treatment of solid tumor. Key words: Solid neoplasms; Colorectal neoplasms; Biliary tract neoplasms; Pancreatic neoplasms; Chimeric antigen receptor T cell; Immunotherapy; Tumor microenvironment