Strategies and challenges in promoting chimeric antigen receptor T cells trafficking and infiltration of solid tumors

The success of chimeric antigen receptor T (CAR-T) cells therapy for hematologic malignancies has sparked interest in potential applications for solid tumors. However, unlike the homogeneous, dynamic, and nutrient-rich hematologic environment, CAR-T cells must overcome the complex tumor microenvironment. Ensuring efficient contact with tumor cells remains a primary challenge to enhance the efficacy of CAR-T cell therapy. Abnormal tumor angiogenesis, disordered chemokine production, dense extracellular matrix, and stromal cells all act as biological barriers that hinder contact of CAR-T cells with tumor cells. This review summarizes specific strategies to promote vascular normalization, modulate chemokine production, target physical barriers, combine different therapeutic approaches, and innovative cell delivery methods to enhance infiltration of CAR-T cells into solid tumors. These strategies will help to overcome current limitations and enhance the effectiveness of CAR-T cell therapy for solid tumors.