A genetically engineered adenovirus vector targeted to CD40 mediates transduction of canine dendritic cells and promotes antigen-specific immune responses in vivo

Erin E. Thacker, Masaharu Nakayama, Bruce F. Smith, R. Curtis Bird, Zhanat Muminova, Theresa V. Strong, Laura Timares, Nikolay Korokhov, Ann Marie O'Neill, Tanja D. de Gruijl, Joel N. Glasgow, Kenzaburo Tani, David T. Curiel

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Targeting viral vectors encoding tumor-associated antigens to dendritic cells (DCs) in vivo is likely to enhance the effectiveness of immunotherapeutic cancer vaccines. We have previously shown that genetic modification of adenovirus (Ad) 5 to incorporate CD40 ligand (CD40L) rather than native fiber allows selective transduction and activation of DCs in vitro. Here, we examine the capacity of this targeted vector to induce immune responses to the tumor antigen CEA in a stringent in vivo canine model. CD40-targeted Ad5 transduced canine DCs via the CD40-CD40L pathway in vitro, and following vaccination of healthy dogs, CD40-targeted Ad5 induced strong anti-CEA cellular and humoral responses. These data validate the canine model for future translational studies and suggest targeting of Ad5 vectors to CD40 for in vivo delivery of tumor antigens to DCs is a feasible approach for successful cancer therapy.

Original languageEnglish
Pages (from-to)7116-7124
Number of pages9
JournalVaccine
Volume27
Issue number50
DOIs
Publication statusPublished - Nov 23 2009

Keywords

  • Adenovirus
  • Cancer immunotherapy
  • Dendritic cell
  • Dog
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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