The tumor microenvironment (TME) is a critical barrier to effective cancer immunotherapy, largely due to the presence of cancer-associated fibroblasts (CAFs) that promote tumor progression and immune suppression. CD105 (endoglin) is highly expressed on CAFs and tumor-associated vasculature, making it a potential target for stromal-directed immunotherapy.

In this study, we developed CD105-targeted chimeric antigen receptor macrophages (CAR-M) to selectively target CAFs. The CAR construct incorporates a CD3ζ intracellular domain to enhance phagocytic activity.

Functionally, CD105 CAR-M exhibited significantly enhanced phagocytosis of CD105-positive CAFs compared to non-transduced macrophages. This indicates effective target recognition and phagocytic activity.

These findings suggest that CD105 CAR-M may contribute to remodeling the tumor microenvironment through selective depletion of CAFs. Further studies are needed to evaluate its impact on immune cell recruitment and anti-tumor efficacy.