Complexes Formed by Mixing Tumor-derived Extracellular Vesicles with Polymeric Surfactants for Personalized Therapeutic Vaccine

Abstract

The personalized therapeutic vaccine is an ideal weapon to eliminate tumors. However, the core steps of manufacturing personalized cancer vaccines are identifying tumor-specific antigens (TSAs, also called neoantigens) and HLA epitope prediction, which is time-consuming and labor-intense. Tumor-derived extracellular vesicles (TEVs) are alternative sources of neoantigens. However, the immunosuppressive nature of TEVs limits their application in such immunotherapy. In this study, we present a new strategy to maintain neoantigens in TEVs and diminish the immunosuppression by deconstructing the structure of TEVs with polymeric surfactant polyethylene glycol-phosphatidylethanolamine (PEG-PE). Together with adjuvant MPLA, the newly formed micelle-like complexes compose a therapeutic vaccine (MLC-V). Results show that MLC-V is capable of eliciting neoantigen-specific T-cell responses, restoring TEV-induced immunosuppression, and preventing lung metastasis of murine melanoma. MLC-V also exhibits outstanding anti-tumor efficacy in multiple tumor models. MLC-V can be used as a personalized therapeutic vaccine in a mimetic pre-clinical MC38 model and the anti-tumor effect of MLC-V was synergistically enhanced by PD-1 mAb. Taken together, the present study demonstrates a time-saving, low-cost, and simplified strategy to produce personalized therapeutic vaccines based on MLC-V platform technology.