Co-delivery of PDL1-blocking scFv and chemotherapeutics using engineered exosomes for cancer therapy

Poor clinical outcomes after immune checkpoint blockers alone may be offset by the combination of chemotherapeutic agents. However, safe, effective and simultaneous delivery of immune checkpoint blockers and chemotherapeutics to tumor cells poses a great challenge. In this study, we took advantage of the low biotoxicity, cargo shielding and immune privilege of exosomes to construct an engineered exosome that can co-deliver chemotherapeutic paclitaxel (PTX) and PDL1-blocking single-chain variable fragments (scFv) specifically to the cancer cells. We demonstrated that the PDL1-blocking scFv expressed on the surface of the exosomes well bound to PD-L1 and significantly reduced the inhibitory effect of PD-L1 on T cells. Moreover, engineered exosomes loaded PTX were more effectively absorbed by the recipient cells as compared to free PTX or control exosomes loaded PTX. In addition, the intravenous injection of APLG-EXO-PTX also inhibited the tumor growth in colon carcinoma xenograft model mice, and showed a significantly increased expression of effector cytokine, IFN-γ indicating that the engineered exosome loaded with PTX could significantly upregulate T-cell activation. The strategy of co-delivering functional scFv and anti-cancer drugs via exosomes heralds a potential approach to improve the effectiveness of cancer treatment in the near future.