PMID- 24225639 OWN - NLM STAT- MEDLINE DCOM- 20140808 LR - 20141120 IS - 1476-5462 (Electronic) IS - 0969-7128 (Linking) VI - 21 IP - 1 DP - 2014 Jan TI - Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. PG - 106-14 LID - 10.1038/gt.2013.65 [doi] AB - For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies. FAU - Kim, E-K AU - Kim EK AD - Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. FAU - Seo, H-S AU - Seo HS AD - WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. FAU - Chae, M-J AU - Chae MJ AD - Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. FAU - Jeon, I-S AU - Jeon IS AD - WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. FAU - Song, B-Y AU - Song BY AD - WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. FAU - Park, Y-J AU - Park YJ AD - Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. FAU - Ahn, H M AU - Ahn HM AD - Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea. FAU - Yun, C-O AU - Yun CO AD - Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea. FAU - Kang, C-Y AU - Kang CY AD - 1] Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea [2] WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131114 PL - England TA - Gene Ther JT - Gene therapy JID - 9421525 RN - 0 (Cancer Vaccines) RN - 0 (HLA-A2 Antigen) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Animals MH - B-Lymphocytes/*immunology/virology MH - *Cancer Vaccines/immunology MH - Cells, Cultured MH - Dependovirus/*genetics/metabolism MH - Female MH - Genetic Vectors MH - HLA-A2 Antigen/immunology MH - Humans MH - Immunotherapy MH - Mammary Neoplasms, Experimental/immunology/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Natural Killer T-Cells/immunology MH - Receptor, ErbB-2/*genetics/metabolism MH - T-Lymphocytes, Cytotoxic/immunology MH - Xenograft Model Antitumor Assays EDAT- 2013/11/15 06:00 MHDA- 2014/08/13 06:00 CRDT- 2013/11/15 06:00 PHST- 2013/05/15 00:00 [received] PHST- 2013/06/14 00:00 [revised] PHST- 2013/09/23 00:00 [accepted] PHST- 2013/11/15 06:00 [entrez] PHST- 2013/11/15 06:00 [pubmed] PHST- 2014/08/13 06:00 [medline] AID - gt201365 [pii] AID - 10.1038/gt.2013.65 [doi] PST - ppublish SO - Gene Ther. 2014 Jan;21(1):106-14. doi: 10.1038/gt.2013.65. Epub 2013 Nov 14.