This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okada, N. Articles by Yamamoto, A. Search for Related Content PubMed PubMed Citation Articles by Okada, N. Articles by Yamamoto, A.

Efficient Antigen Gene Transduction Using Arg-Gly-Asp Fiber-Mutant Adenovirus Vectors Can Potentiate Antitumor Vaccine Efficacy and Maturation of Murine Dendritic Cells¹

Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto 607-8414 [N. O., T. S., Y. M., K. M., T. F., A. Y.]; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 [Y. T., S. N., T. M.]; Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501 [H. M., T. H.]; and Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women’s University, Hyogo 663-8179 [Y. O.], Japan

Dendritic cells (DCs), the most effective antigen-presenting cells, are being studied as adjuvants or antigen delivery vehicles for eliciting T-cell-mediated antitumor immunity. Gene delivery to DCs provides an intracellular source of antigen for efficient and persistent loading to MHC class I molecules capable of activating CD8⁺ CTLs, which play a central role in antitumor immunity. We previously reported that the fiber-mutant adenovirus vector (Ad) harboring the Arg-Gly-Asp (RGD) sequence in the HI loop of its fiber knob could more efficiently transduce the LacZ gene into both murine DC lines and normal human DCs than conventional Ad. In the present study, we compared immunological properties and vaccine efficacy of DC2.4 cells, an immature murine DC line, transduced with an ovalbumin (OVA) gene by fiber-mutant Ad (Ad-RGD-OVA) or conventional Ad (Ad-OVA). Ad-RGD-OVA-infected DC2.4 cells could more efficiently present OVA peptides via MHC class I molecules in a vector particle-dependent manner and induce OVA-specific CTL response by vaccination than Ad-OVA-infected DC2.4 cells. This result was correlated with the efficiency of gene transduction into DC2.4 cells by both types of Ad. Moreover, vaccination with Ad-RGD-OVA-infected DC2.4 cells could achieve an equal or greater antitumor effect against challenge with E.G7-OVA tumor cells with lower doses of Ad on infection or fewer cells for immunization than the vaccination procedure using Ad-OVA-infected DC2.4 cells. In addition, the maturation of DC2.4 cells was promoted by efficient expression of the antigen gene by the Arg-Gly-Asp fiber-mutant Ad. Flow cytometric analysis indicated enhanced expression of MHC class I and II molecules as well as CD80, CD86, CD40, and CD54, and reverse transcription-PCR analysis revealed increased levels of interleukin 12 p40 mRNA. However, infection by Ad-OVA or Ad that did not contain the cDNA of interest (Ad-Null and Ad-RGD-Null) contributed little to phenotypical changes in DC2.4 cells. On the basis of these results, we propose that DC manipulation using the Arg-Gly-Asp fiber-mutant Ad system could advance the development of more effective vaccines and allow for more convenient administration of DC-based gene immunotherapy.

This article has been cited by other articles:

				S. Worgall, A. Krause, J. Qiu, J. Joh, N. R. Hackett, and R. G. Crystal Protective Immunity to Pseudomonas aeruginosa Induced with a Capsid-Modified Adenovirus Expressing P. aeruginosa OprF J. Virol., December 15, 2007; 81(24): 13801 - 13808. [Abstract] [Full Text] [PDF]

				A. Krause, J. H. Joh, N. R. Hackett, P. W. Roelvink, J. T. Bruder, T. J. Wickham, I. Kovesdi, R. G. Crystal, and S. Worgall Epitopes Expressed in Different Adenovirus Capsid Proteins Induce Different Levels of Epitope-Specific Immunity J. Virol., June 1, 2006; 80(11): 5523 - 5530. [Abstract] [Full Text] [PDF]

				A. Harui, M. D. Roth, D. Vira, M. Sanghvi, H. Mizuguchi, and S. K. Basak Adenoviral-encoded antigens are presented efficiently by a subset of dendritic cells expressing high levels of {alpha}v{beta}3 integrins J. Leukoc. Biol., June 1, 2006; 79(6): 1271 - 1278. [Abstract] [Full Text] [PDF]

				H. Jing, J.-H. Yen, and D. Ganea A Novel Signaling Pathway Mediates the Inhibition of CCL3/4 Expression by Prostaglandin E2 J. Biol. Chem., December 31, 2004; 279(53): 55176 - 55186. [Abstract] [Full Text] [PDF]

				M. S. Aguzzi, C. Giampietri, F. De Marchis, F. Padula, R. Gaeta, G. Ragone, M. C. Capogrossi, and A. Facchiano RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells Blood, June 1, 2004; 103(11): 4180 - 4187. [Abstract] [Full Text] [PDF]

				S. Worgall, A. Busch, M. Rivara, D. Bonnyay, P. L. Leopold, R. Merritt, N. R. Hackett, P. W. Rovelink, J. T. Bruder, T. J. Wickham, et al. Modification to the Capsid of the Adenovirus Vector That Enhances Dendritic Cell Infection and Transgene-Specific Cellular Immune Responses J. Virol., March 1, 2004; 78(5): 2572 - 2580. [Abstract] [Full Text] [PDF]

				J.-Q. Gao, Y. Tsuda, K. Katayama, T. Nakayama, Y. Hatanaka, Y. Tani, H. Mizuguchi, T. Hayakawa, O. Yoshie, Y. Tsutsumi, et al. Antitumor Effect by Interleukin-11 Receptor {alpha}-Locus Chemokine/CCL27, Introduced into Tumor Cells through a Recombinant Adenovirus Vector Cancer Res., August 1, 2003; 63(15): 4420 - 4425. [Abstract] [Full Text] [PDF]