Oncotarget

Research Papers: Immunology:

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

Viswa Teja Colluru, Douglas G. McNeel _

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Oncotarget. 2016; 7:67901-67918. https://doi.org/10.18632/oncotarget.12178

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Abstract

Viswa Teja Colluru1,2 and Douglas G. McNeel1,2

1 Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA

2 Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA

Correspondence to:

Douglas G. McNeel, email:

Keywords: DNA vaccine, B cells, dendritic cells, direct presentation, Immunology and Microbiology Section, Immune response, Immunity

Received: July 26, 2016 Accepted: September 16, 2016 Published: September 21, 2016

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.


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