1. ¹Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan
2. ²Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Saito-Asagi, Ibaraki, Osaka, Japan

Correspondence: Dr S Nakagawa, Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: nakagawa@phs.osaka-u.ac.jp; Dr N Okada, E-mail: okada@phs.osaka-u.ac.jp

³Current address: Center for Advanced Research and Education in Drug Discovery and Development, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.

Received 26 January 2008; Revised 2 March 2008; Accepted 2 March 2008; Published online 15 May 2008.

Abstract

Dendritic cells (DCs) have a critical role in the induction of antigen-specific immune responses, transporting antigens from peripheral tissue to regional lymph nodes where they interact with antigen-specific T lymphocytes. Recent studies revealed that the efficacy of the T cell-dependent immune response depends on the lifespan of the antigen-presenting DCs in the lymph nodes. Here, we succeeded in engineering long-lived antigen-presenting DCs via Bcl-x_L-derived hyperactive mutant antiapoptotic protein (Bcl-x_FNK) gene transfer. In a B16BL6 melanoma model, these long-lived DCs exerted potent antitumor immunity that depended mainly on antigen-specific cytotoxic T lymphocytes. Furthermore, in vivo longevity of the long-lived DC vaccine led to antigen-specific activation of interferon--producing CD4⁺ and CD8⁺ T cells. Thus, the long-lived DC vaccine strategy is highly useful for constructing DC vaccines, as well as other cell-based medicines, such as stem cell therapy.