PMID- 19238013 OWN - NLM STAT- MEDLINE DCOM- 20090406 LR - 20220914 IS - 1537-4513 (Electronic) IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 32 IP - 2 DP - 2009 Feb-Mar TI - Targeting the intratumoral dendritic cells by the oncolytic adenoviral vaccine expressing RANTES elicits potent antitumor immunity. PG - 145-56 LID - 10.1097/CJI.0b013e318193d31e [doi] AB - Dendritic cells (DCs) are professional antigen (Ag)-presenting cells capable of inducing immune responses to tumor Ags and, therefore, play a central role in the induction of antitumor immunity. There is a large amount of evidence, however, about paucity of tumor-associated DCs and that DCs' immunogenic functions are suppressed in a tumor environment. Here we describe a potent in situ vaccine targeting tumoral DCs in vivo. This vaccine comprised of an oncolytic adenovirus expressing RANTES (regulated upon activation, normally T expressed, and presumably secreted) (Ad-RANTES-E1A), enhanced tumor infiltration, and maturation of Ag-presenting cells in vivo. In this study, we show that intratumoral vaccinations with Ad-RANTES-E1A induced significant primary tumor growth regression and blocked metastasis formation in JC and E.G-7 murine tumor models. This vaccine recruited DCs, macrophages, natural killer cells, and CD8+ T cells to the tumor site, and thus enhanced Ag-specific cytotoxic T lymphocyte responses and natural killer cell responses. DCs purified from the Ad-RANTES-E1A-treated E.G-7 tumors secreted significantly higher levels of interferon-gamma and interleukin-12, as compared with control groups and more efficiently enhanced CD8+ T-cell response. This in situ immunization strategy could be a potent antitumor immunotherapy approach for aggressive established tumors. FAU - Lapteva, Natalia AU - Lapteva N AD - Center for Cell and Gene Therapy, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. FAU - Aldrich, Melissa AU - Aldrich M FAU - Weksberg, David AU - Weksberg D FAU - Rollins, Lisa AU - Rollins L FAU - Goltsova, Tatiana AU - Goltsova T FAU - Chen, Si-Yi AU - Chen SY FAU - Huang, Xue F AU - Huang XF LA - eng GR - R01AI68472/AI/NIAID NIH HHS/United States GR - R01 CA116677/CA/NCI NIH HHS/United States GR - R01 AI068472/AI/NIAID NIH HHS/United States GR - R01 CA11667/CA/NCI NIH HHS/United States GR - R01 CA090427/CA/NCI NIH HHS/United States GR - R01 CA90427/CA/NCI NIH HHS/United States GR - R01 CA100841/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Cancer Vaccines) RN - 0 (Chemokine CCL5) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Adenoviridae/genetics/immunology MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology/metabolism MH - Cancer Vaccines/genetics/immunology/*therapeutic use MH - Chemokine CCL5/*genetics/immunology MH - Dendritic Cells/*immunology/virology MH - Female MH - Genetic Vectors/immunology MH - Immunotherapy MH - Interferon-gamma/blood MH - Interleukin-12/blood MH - Killer Cells, Natural/immunology/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Neoplasms/genetics/*therapy/virology MH - Oncolytic Virotherapy MH - Oncolytic Viruses/genetics/*immunology MH - Ovalbumin/immunology PMC - PMC4146345 MID - NIHMS622209 EDAT- 2009/02/25 09:00 MHDA- 2009/04/07 09:00 PMCR- 2014/08/27 CRDT- 2009/02/25 09:00 PHST- 2009/02/25 09:00 [entrez] PHST- 2009/02/25 09:00 [pubmed] PHST- 2009/04/07 09:00 [medline] PHST- 2014/08/27 00:00 [pmc-release] AID - 00002371-200902000-00006 [pii] AID - 10.1097/CJI.0b013e318193d31e [doi] PST - ppublish SO - J Immunother. 2009 Feb-Mar;32(2):145-56. doi: 10.1097/CJI.0b013e318193d31e.