In vivo delivery of antigens by adenovirus dodecahedron induces cellular and humoral immune responses to elicit antitumor immunity

Mol Ther. 2010 May;18(5):1046-53. doi: 10.1038/mt.2010.16. Epub 2010 Feb 23.


Cancer vaccines based on virus-like particles (VLPs) vectors may offer many advantages over other antigen-delivery systems and represent an alternative to the ex vivo cell therapy approach. In this study, we describe the use of penton-dodecahedron (Pt-Dd) VLPs from human adenovirus type 3 (Ad3) as cancer vaccine vehicle for specific antigens, based on its unique cellular internalization properties. WW domains from the ubiquitin ligase Nedd4 serve as an adapter to bind the antigen to Pt-Dd. By engineering fusion partners of WW with the model antigen ovalbumin (OVA), Pt-Dd can efficiently deliver WW-OVA in vitro and the Pt-Dd/WW complex can be readily internalized by dendritic cells (DCs). Immunization with WW-OVA/Pt-Dd results in 90% protection against B16-OVA melanoma implantation in syngeneic mice. This high level of protection correlates with the development of OVA-specific CD8(+) T cells. Moreover, vaccination with WW-OVA Pt-Dd induces robust humoral responses in mice as shown by the high levels of anti-OVA antibodies (Abs) detected in serum. Importantly, treatment of mice bearing B16-OVA tumors with WW-OVA/Pt-Dd results in complete tumor regression in 100% of cases. Thus, our data supports a dual role of Pt-Dd as antigen-delivery vector and natural adjuvant, able to generate integrated cellular and humoral responses of broad immunogenic complexity to elicit specific antitumor immunity. Antigen delivery by Pt-Dd vector is a promising novel strategy for development of cancer vaccines with important clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use*
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • HeLa Cells
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Immunotherapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Inbred C57BL
  • Nedd4 Ubiquitin Protein Ligases
  • Ovalbumin / immunology*
  • Ubiquitin-Protein Ligases / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / immunology*


  • Cancer Vaccines
  • Endosomal Sorting Complexes Required for Transport
  • Viral Proteins
  • Ovalbumin
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Nedd4l protein, mouse
  • Ubiquitin-Protein Ligases