Abstract

This proposal explores the utilization of adenoviral vectors targeted dendritic cells (DC) for the expression of a tumor specific antigen as a means to induce maturation and antigen presentation of these cells to elicit a primary antitumor response. The key element of this study is the CD40 targeting and simultaneous stimulation of the DCs using a modified adenoviral vector possessing altered tropism. The efficacy of the vector transduced DC-based vaccination will be assessed. The validity of this proposal is based on numerous recent publications advancing the progress towards vaccination-based adjuvant therapies using antigen primed DCs and the development and understanding of the role that DCs play in the presentation of antigen to elicit cellular and humor immune responses. Ultimately, advances made during this study will help in translating the current knowledge into clinical practice for the treatment of cancer by inducing a tumor-specific immune response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA086881-05
Application #
6759351
Study Section
Medical Biochemistry Study Section (MEDB)
Program Officer
Hecht, Toby T
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2004-09-15
Budget End
2005-06-30
Support Year
5
Fiscal Year
2004
Total Cost
$226,013
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Hangalapura, Basav N; Oosterhoff, Dinja; Gupta, Tarun et al. (2011) Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an adenovirus based melanoma vaccine. Vaccine 29:2313-21
Chen, Jian; Hsu, Hui-Chen; Zajac, Allan J et al. (2006) In vivo analysis of adenovirus-specific cytotoxic T lymphocyte response in mice deficient in CD28, fas ligand, and perforin. Hum Gene Ther 17:669-82
Breidenbach, Martina; Rein, Daniel T; Schondorf, Thomas et al. (2006) A new targeting approach for breast cancer gene therapy using the heparanase promoter. Cancer Lett 240:114-22
Gommans, W M; van Eert, S J; McLaughlin, P M J et al. (2006) The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and selective gene expression in an adenoviral context. Cancer Gene Ther 13:150-8
Noureddini, Sam C; Krendelshchikov, Alexander; Simonenko, Vera et al. (2006) Generation and selection of targeted adenoviruses embodying optimized vector properties. Virus Res 116:185-95
Volk, Andrea L; Rivera, Angel A; Page, Grier P et al. (2005) Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways. Cancer Gene Ther 12:162-74
Korokhov, Nikolay; Noureddini, Sam C; Curiel, David T et al. (2005) A single-component CD40-targeted adenovirus vector displays highly efficient transduction and activation of dendritic cells in a human skin substrate system. Mol Pharm 2:218-23
Wu, Hongju; Han, Tie; Belousova, Natalya et al. (2005) Identification of sites in adenovirus hexon for foreign peptide incorporation. J Virol 79:3382-90
Chen, J; Zajac, A J; McPherson, S A et al. (2005) Primary adenovirus-specific cytotoxic T lymphocyte response occurs after viral clearance and liver enzyme elevation. Gene Ther 12:1079-88
Izumi, Miiru; Kawakami, Yosuke; Glasgow, Joel N et al. (2005) In vivo analysis of a genetically modified adenoviral vector targeted to human CD40 using a novel transient transgenic model. J Gene Med 7:1517-25

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