PMID- 18480845 OWN - NLM STAT- MEDLINE DCOM- 20081204 LR - 20201222 IS - 1476-5462 (Electronic) IS - 0969-7128 (Linking) VI - 15 IP - 19 DP - 2008 Oct TI - Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency. PG - 1321-9 LID - 10.1038/gt.2008.85 [doi] AB - 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-XL-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-gamma-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. FAU - Yoshikawa, T AU - Yoshikawa T AD - Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan. FAU - Niwa, T AU - Niwa T FAU - Mizuguchi, H AU - Mizuguchi H FAU - Okada, N AU - Okada N FAU - Nakagawa, S AU - Nakagawa S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080515 PL - England TA - Gene Ther JT - Gene therapy JID - 9421525 RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Movement MH - Cell Survival MH - Dendritic Cells/*immunology MH - Female MH - Genetic Engineering MH - Genetic Therapy/*methods MH - Immunotherapy, Adoptive/*methods MH - Interferon-gamma/immunology MH - Melanoma, Experimental/immunology/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Neoplasm Transplantation MH - Skin Neoplasms/immunology/*therapy MH - Transduction, Genetic/methods EDAT- 2008/05/16 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/05/16 09:00 PHST- 2008/05/16 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/05/16 09:00 [entrez] AID - gt200885 [pii] AID - 10.1038/gt.2008.85 [doi] PST - ppublish SO - Gene Ther. 2008 Oct;15(19):1321-9. doi: 10.1038/gt.2008.85. Epub 2008 May 15.