Cell membranes have recently gained attention as a promising drug delivery system. Here, dendritic cell membrane vesicles (DC‐MVs) are examined as a platform to promote T cell responses. Nanosized DC‐MVs are derived from DCs pretreated with monophosphoryl lipid A (MPLA), a FDA‐approved immunostimulatory adjuvant. These “mature” DC‐MVs activate DCs in vitro and increase their expression of costimulatory markers. DC‐MVs also promote cross‐priming of antigen‐specific T cells in vitro, increasing their survival and CD25 expression. In addition, these mature DC‐MVs potently augment the expansion of adoptively transferred CD8+ T cells in vivo, generating twofold to fourfold higher frequency of antigen‐specific T cells, compared with other control formulations, including “immature” DC‐MVs obtained without the MPLA pretreatment. Taken together, these results suggest that DC‐MVs are an effective delivery platform for T cell activation and may serve as a potential delivery system for improving adoptive T cell therapy.
- Award ID(s):
- 1648035
- NSF-PAR ID:
- 10311294
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Editor(s):
- Nikolich-Žugich, Janko
- Date Published:
- Journal Name:
- PLOS Pathogens
- Volume:
- 17
- Issue:
- 1
- ISSN:
- 1553-7374
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
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Methods To test this hypothesis, we administered intracellular delivering (ID) Salmonella that deliver ovalbumin as a model antigen into tumor-bearing, ovalbumin-vaccinated mice. ID Salmonella delivers antigens by autonomously lysing in cells after the induction of cell invasion.
Results We showed that the delivered ovalbumin disperses throughout the cytoplasm of cells in culture and in tumors. This delivery into the cytoplasm is essential for antigen cross-presentation. We showed that co-culture of ovalbumin-recipient cancer cells with ovalbumin-specific CD8 T cells triggered a cytotoxic T cell response. After the adoptive transfer of OT-I CD8 T cells, intracellular delivery of ovalbumin reduced tumor growth and eliminated tumors. This effect was dependent on the presence of the ovalbumin-specific T cells. Following vaccination with the exogenous antigen in mice, intracellular delivery of the antigen cleared 43% of established KPC pancreatic tumors, increased survival, and prevented tumor re-implantation.
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