Journal
ADVANCED HEALTHCARE MATERIALS
Volume 8, Issue 4, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201801091
Keywords
membrane vesicles; peptide antigens; T cell activation; vaccines
Funding
- NIH [R01AI127070, R01EB022563, R01CA210273]
- Emerald Foundation
- Melanoma Research Alliance [348774]
- DoD/CDMRP Peer Reviewed Cancer Research Program [W81XWH-16-1-0369]
- NSF CAREER Award [1553831]
- UM Rackham
- AFPE
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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.
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