Scheme 1

Schematic illustration of targeted delivery of a PD1-TREM2 scFv by CAR-T cells to enhances anti-tumor efficacy in colorectal cancer. First, the lentivirus encoding CART-CEA.sBsAb was generated using a three-plasmid lentiviral packing system. Mouse T cells were transduced with the encoding CART-CEA.sBsAb, and the successful preparation of autocrine PD-1-TREM2 scFv CAR-T cells (CART-CEA.sBsAb) was achieved. The anti-tumor mechanism of CART-CEA.sBsAb was evaluated in a subcutaneous CRC mouse model. The PD-1-TREM2 scFv secreted by CAR-T cells remained localized within tumors and blocked the PD-1/PD-L1 pathway and the binding of ligands to TREM2 receptors present on MDSCs and TAMs; the percentages of MDSCs and TAMs were decreased, and the levels of TNF-α, IFN-γ, IL-2, granzyme B, and perforin were enhanced. Finally, the intratumoral proportion and cytotoxic ability of CART-CEA.sBsAb increased