1. ¹Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan
2. ²Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3. ³Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
4. ⁴Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan
5. ⁵National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan
6. ⁶Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

Correspondence: Dr N Okada, Department of Biopharmaceutics, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan

Received 15 April 2004; Accepted 5 July 2004; Published online 14 October 2004.

Abstract

Although dendritic cell (DC)-based immunotherapy is considered a promising approach for cancer treatment, a large quantity of DC vaccine is required for effective sensitization/activation of immune cells because of the poor migratory ability of administered DCs into regional lymphoid tissue. In this study, we created a DC vaccine sufficiently transduced with CC chemokine receptor-7 gene (CCR7/DCs) by applying RGD fiber-mutant adenovirus vector (AdRGD), and investigated its immunological characteristics and therapeutic efficacy. CCR7/DCs acquired strong chemotactic activity for CC chemokine ligand-21 (CCL21) and exhibited an immunophenotype similar to mature DCs but not immature DCs with regard to major histocompatibility complex/costimulatory molecule-expression levels and allogenic T cell proliferation-stimulating ability, while maintaining inherent endocytotic activity. Importantly, CCR7/DCs injected intradermally into mice could accumulate in draining lymph nodes about 5.5-fold more efficiently than control AdRGD-applied DCs. Reflecting these properties of CCR7/DCs, DC vaccine genetically engineered to simultaneously express endogenous antigen and CCR7 could elicit more effective antigen-specific immune response in vivo using a lower dosage than DC vaccine transduced with antigen alone. Therefore, the application of CCR7/DCs having positive migratory ability to lymphoid tissues may contribute to reduction of efforts and costs associated with DC vaccine preparation by considerably reducing the DC vaccine dosage needed to achieve effective treatment by DC-based immunotherapy.