Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma

Fibroblast activation protein (FAP) is a membrane protease that is highly expressed by cancer-associated fibroblasts (CAFs). FAP can modulate the tumor microenvironment (TME) by remodeling the extracellular matrix (ECM), and its overexpression on CAFs is associated with poor prognosis in various cancers. The TME is in part accountable for the limited efficacy of chimeric antigen receptor (CAR)-T cell therapy in treatment of solid tumors. Targeting FAP with CAR-T cells is one of the strategies being researched to overcome the challenges in the TME. This review describes the role of FAP in the TME and its potential as a target in CAR-T cell immunotherapy, summarizes the preclinical studies and clinical trials of anti-FAP-CAR-T cells to date, and reviews possible optimizations to augment their cytotoxic efficiency in solid tumors.

Automated summary

FAP, a membrane protease highly expressed by cancer-associated fibroblasts, plays a role in modulating the tumor microenvironment by remodeling the extracellular matrix, with its overexpression associated with poor prognosis in various cancers. Limited efficacy of CAR-T cell therapy in solid tumors is partially due to the challenges presented by the TME. Targeting FAP with CAR-T cells is a strategy being researched to potentially enhance cytotoxic efficiency in solid tumors.