Allogenicity Boosts Extracellular Vesicle-Induced Antigen-Specific Immunity and Mediates Tumor Protection and Long-Term Memory In Vivo

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2019-08, Vol.203 (4), p.825-834
Main Authors: Larssen, Pia, Veerman, Rosanne E, Akpinar, Gözde Güçlüler, Hiltbrunner, Stefanie, Karlsson, Mikael C I, Gabrielsson, Susanne
Format: Article
Language:English
Subjects:
Allografts
Animals
Bone Marrow Cells - immunology
Dendritic Cells - immunology
Extracellular Vesicles - immunology
Extracellular Vesicles - transplantation
Immunologic Memory - immunology
Immunotherapy - methods
Isografts
Medicin och hälsovetenskap
Melanoma, Experimental - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
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Summary: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.
ISSN:0022-1767
1550-6606
1550-6606
DOI:10.4049/jimmunol.1801628