Dexosomes as a cell-free vaccine for cancer immunotherapy

Abstract

Dendritic cells (DCs) secrete vast quantities of exosomes termed as dexosomes. Dexosomes are symmetric nanoscale heat-stable vesicles that consist of a lipid bilayer displaying a characteristic series of lipid and protein molecules. They include tetraspanins and all established proteins for presenting antigenic material such as the major histocompatibility complex class I/II (MHC I/II) and CD1a, b, c, d proteins and CD86 costimulatory molecule. Dexosomes contribute to antigen-specific cellular immune responses by incorporating the MHC proteins with antigen molecules and transferring the antigen-MHC complexes and other associated molecules to naïve DCs. A variety of ex vivo and in vivo studies demonstrated that antigen-loaded dexosomes were able to initiate potent antitumor immunity. Human dexosomes can be easily prepared using monocyte-derived DCs isolated by leukapheresis of peripheral blood and treated ex vivo by cytokines and other factors. The feasibility of implementing dexosomes as therapeutic antitumor vaccines has been verified in two phase I and one phase II clinical trials in malignant melanoma and non small cell lung carcinoma patients. These studies proved the safety of dexosome administration and showed that dexosome vaccines have the capacity to trigger both the adaptive (T lymphocytes) and the innate (natural killer cells) immune cell recalls. In the current review, we will focus on the perspective of utilizing dexosome vaccines in the context of cancer immunotherapy.

Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope

“…For the first time, exosomes, as natural carriers of mRNAand microRNA-, were discovered in mast cells by Valadi et al [14]. Exosomes were also detected as an important carrier of intracellular signaling in several other cells [15,16]. Due to the biocompatibility nature of extracellular vesicles (EVs) with human cells, they successfully cross the cellular membrane and bypass drug delivery obstacles, including RNase degradation, endosomal accumulation, phagocytosis, multidrug resistance, cytotoxicity, and immunogenicity [17,18].…”

Exosome-Based Vaccines: History, Current State, and Clinical Trials

“…The direct interaction of DEXs with T cells seems to demonstrate poor efficiency in stimulating T cell responses, therefore DEXs have less T cell stimulation potential than their parent DCs (66,84). Some authors suggest that exosomes are not able to interact directly with effector cells, thus prior capturing and processing the exosomes by DCs is a superior pathway of priming specific T cells via DEXs (75,81,85,86). A study using the direct interaction of DEXs with T cells showed that DEXs from mature DCs are better at stimulating T cells than DEXs from immature DCs (87).…”

Small extracellular vesicles in cancer

“…To prime the immune response against a tumor, a specific subset of T-lymphocytes, the CD8 + T-cells, need to be activated. Priming of naïve CD8 + T-cells requires stimulation of the T-cell receptor (TCR) with the antigen-loaded MHCI of the APC and co-stimulation of APC CD80 and CD28 of the naïve CD8 + T-cell [ 507 ]. This results in proliferation of the cytotoxic lymphocyte (CTL).…”