Fibroblast activation protein constitutes a novel target of chimeric antigen receptor T-cell therapy in solid tumors

With recent advances in tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has achieved unprecedented success in several hematologic tumors, significantly improving patient prognosis. However, in solid tumors, the efficacy of CAR-T cell therapy is limited because of high antigen uncertainty and the extremely restrictive tumor microenvironment (TME). This challenge has led to the exploration of new targets, among which fibroblast activation protein (FAP) has gained attention for its relatively stable and specific expression in the TME of various solid tumors, making it a potential new target for CAR-T cell therapy. This study comprehensively analyzed the biological characteristics of FAP and discussed its potential application in CAR-T cell therapy, including the theoretical basis, and preclinical and clinical research progress of targeting FAP with CAR-T cell therapy for solid tumor treatment. The challenges and future optimization directions of this treatment strategy were also explored, providing new perspectives and strategies for CAR-T cell therapy in solid tumors. Cancer-associated fibroblasts (CAFs) in the complex tumor microenvironment of solid tumors. Characterized by the consistent expression of fibroblast activation protein (FAP), The targeting of FAP+CAFs with CAR-T-cell therapy emerges as a promising strategy, offering the potential to disrupt these defensive fortifications and significantly enhance the efficacy of immunotherapy in the battle against solid tumors.image