Harnessing the exosome-induced immune response for cancer immunotherapy

Abstract

In recent years exosomes have emerged as potent stimulators of immune responses and as agents for cancer therapy. Exosomes can carry a broad variety of immunostimulatory molecules depending on the cell of origin and in vitro culture conditions. Dendritic cell-derived exosomes (dexosomes) have been shown to carry NK cell activating ligands and can be loaded with antigen to activate invariant NKT cells and to induce antigen-specific T and B cell responses. Dexosomes have been investigated as therapeutic agents against cancer in two phase I clinical trials, with a phase II clinical trial currently ongoing. Dexosomes were well tolerated but therapeutic success and immune activation were limited. Several reports suggest that multiple factors need to be considered in order to improve exosomal immunogenicity for cancer immunotherapy. These include antigen-loading strategies, exosome composition and exosomal trafficking in vivo. Hence, a better understanding of how to engineer and deliver exosomes to specific cells is crucial to generate strong immune responses and to improve the immunotherapeutic potential of exosomes.

Keywords: Adaptive immunity; Cancer immunotherapy; Dendritic cells; Exosomes; Innate immunity.