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Oncotarget. 2016 Oct 18;7(42):67901-67918. doi: 10.18632/oncotarget.12178.

B lymphocytes as direct antigen-presenting cells for anti-tumor DNA vaccines.

Author information

1
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
2
Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.

Abstract

In spite of remarkable preclinical efficacy, DNA vaccination has demonstrated low immunogenicity in humans. While efforts have focused on increasing cross-presentation of DNA-encoded antigens, efforts to increase DNA vaccine immunogenicity by targeting direct presentation have remained mostly unexplored. In these studies, we compared the ability of different APCs to present antigen to T cells after simple co-culture with plasmid DNA. We found that human primary peripheral B lymphocytes, and not monocytes or in vitro derived dendritic cells (DCs), were able to efficiently encode antigen mRNA and expand cognate tumor antigen-specific CD8 T cells ex vivo. Similarly, murine B lymphocytes co-cultured with plasmid DNA, and not DCs, were able to prime antigen-specific T cells in vivo. Moreover, B lymphocyte-mediated presentation of plasmid antigen led to greater Th1-biased immunity and was sufficient to elicit an anti-tumor effect in vivo. Surprisingly, increasing plasmid presentation by B cells, and not cross presentation of peptides by DCs, further augmented traditional plasmid vaccination. Together, these data suggest that targeting plasmid DNA to B lymphocytes, for example through transfer of ex vivo plasmidloaded B cells, may be novel means to achieve greater T cell immunity from DNA vaccines.

KEYWORDS:

B cells; DNA vaccine; Immune response; Immunity; Immunology and Microbiology Section; dendritic cells; direct presentation

PMID:
27661128
PMCID:
PMC5356528
DOI:
10.18632/oncotarget.12178
[Indexed for MEDLINE]
Free PMC Article

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