Fig. 3.

Increasing CAR T cell trafficking to the tumor site. Tumor cells in the tumor microenvironment (TME) can secrete large quantities of chemokines. Identifying the most highly secreted chemokines in the targeted tumor and overexpression of the corresponding chemokine receptors on CAR T cells can improve their trafficking ability to tumor sites. Tumor blood vessels and extracellular matrix (ECM) are the main physical barriers hindering the infiltration of CAR T cells. VEGFR2-CAR T cells can destroy tumor vascular endothelial cells to increase penetration. FAP-CAR T cells can inhibit stromagenesis and angiogenesis by targeting FAP⁺ CASCs. CAR T cells expressing heparanase can degrade heparan sulfate proteoglycan to disrupt the ECM