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J Immunol. 2019 Jul 10. pii: ji1801628. doi: 10.4049/jimmunol.1801628. [Epub ahead of print]

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

Author information

1
Division of Immunology and Allergy, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 64 Stockholm, Sweden; and.
2
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
3
Division of Immunology and Allergy, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 64 Stockholm, Sweden; and Susanne.Gabrielsson@ki.se.

Abstract

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.

PMID:
31292216
DOI:
10.4049/jimmunol.1801628

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