Efficient cancer immunogenetherapy by tumor cell lysate modified mRNA formulation.

Abstract

mRNA-based gene therapy has an important role in cancer therapy. Intensive attention has been paid to investigate mRNA-delivery systems with high efficiency of delivery, but few studies have explored the immunotherapeutic capacity of the delivery vector. A tumor cell lysate represents an ideal resource for constructing advanced mRNA-delivery systems with immunostimulatory potential. However, the limited room of mRNA vectors and the complex composition of the cancer cell lysate are obstacles to their combined function. In this study, we present a novel tumor cell lysate-based mRNA delivery system, TLSV/IL-17A (tumor cell lysate vehicles carrying interleukin (IL)-17A-coded mRNA). TLSV demonstrates high mRNA delivery efficiency in both dendritic cells (DCs) and tumor cells. It triggers a robust anti-cancer immune response by specifically activating plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells. By loading IL-17A mRNA, the TLSV/IL-17A effectively inhibits multiple colon cancer models. Our results demonstrate the therapeutic potential of TLSV system in tumor immunogenetherapy.