Publication date: Jul 10, 2019
Extracellular vesicles (EV) are candidates for cancer immunotherapy because of their capacity to stimulate tumor-specific activity in vivo. However, clinical trials using peptide-loaded autologous EVs have so far only showed moderate T cell responses, suggesting a need for optimization of EV-induced immunity in humans. We previously demonstrated that induction of Ag-specific CD8 T cells and antitumor responses to whole Ag were independent of MHC class I on EVs and hypothesized that multiple injections of allogeneic EVs could potentiate Ag-specific responses. In this study, we show that the allogeneic EV from mouse bone marrow-derived dendritic cells enhances Ag-specific CD8 T cell, follicular helper T cell, and Ag-specific Ab responses. EV-injected mice demonstrated Ag-specific memory after 4 mo, with the highest Ab avidity in mice receiving double allogeneic EV injections. Reduced B16mOVA melanoma tumor growth was shown in all EV-injected groups. Our findings support the application of allogeneic EVs for therapeutic use in clinical studies in which an adaptive immune response is desired.
Larssen, P., Veerman, R.E., Akpinar, G.G., Hiltbrunner, S., Karlsson, M.C.I., and Gabrielsson, S. Allogenicity Boosts Extracellular Vesicle-Induced Antigen-Specific Immunity and Mediates Tumor Protection and Long-Term Memory In Vivo. 23353. 2019 J Immunol.
- Melanoma-derived extracellular vesicles instigate pro-inflammatory signaling in the metastatic microenvironment.