Incorporation of porcine adenovirus 4 fiber protein enhances infectivity of adenovirus vector on dendritic cells: Implications for immune-mediated cancer therapy

I Wilkinson-Ryan,J Kim,S Kim,M.A Powell,D.G Mutch,D Spitzer,T Hansen,S.P Goedebeuure,D.T Curiel,W Hawkins

doi:10.1016/j.ygyno.2014.03.278

Abstract

Incorporation of porcine adenovirus 4 fiber protein enhances infectivity of adenovirus vector on dendritic cells: Implications for immune-mediated cancer therapy

Highlights

Dendritic cells (DCs) can be engineered to yield a clinical benefit when an antigen is delivered directly to DCs for presentation and immune stimulation [1,2,3,4]
Recent studies have shown that the CD141+ DC subset in humans, which is equivalent to the CD8α+ subset in mice, is the most efficient at cross-presenting antigens on MHC I to naïve CD8+ T-cells, which is essential for cytotoxic T lymphocytes (CTL)—mediated immune responses to viruses and tumor antigens [2,4,6]
To investigate infection efficiency of Ad5-porcine fiber knob (PK) in immature dendritic cells, the gene transfer assay was performed with a panel of genetically modified adenoviruses that are currently undergoing study for clinical application: Ad5Luc1, DC infectivity enhanced Ad5/3Luc1, DC targeted Ad5Luc.FF/CD40L, and Ad5Luc1-PK

Summary

Introduction

Dendritic cells (DCs) can be engineered to yield a clinical benefit when an antigen is delivered directly to DCs for presentation and immune stimulation [1,2,3,4]. DCs loaded with tumor associated antigens can prime and activate T-cells to mount an anti-tumor immune response. One potential pitfall of DC mediated immunotherapy is inadequate antigen loading as well as antigen expression by regulatory DC subsets, which can lead to immune tolerance [5]. Antigen delivery systems must result in high levels of expression by the proper DC subsets to avoid tolerance. Recent studies have shown that the CD141+ (or BDCA3+) DC subset in humans, which is equivalent to the CD8α+ subset in mice, is the most efficient at cross-presenting antigens on MHC I to naïve CD8+ T-cells, which is essential for cytotoxic T lymphocytes (CTL)—mediated immune responses to viruses and tumor antigens [2,4,6]. DC manipulation is under investigation for a variety of cancers and represents a promising vehicle for cancer immunotherapy [1,2,3,4,7,9,10]

Objectives

Methods

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Conclusion