Targeting the intratumoral dendritic cells by the oncolytic adenoviral vaccine expressing RANTES elicits potent antitumor immunity.
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.
Lapteva
Natalia
N
Center for Cell and Gene Therapy, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Aldrich
Melissa
M
Weksberg
David
D
Rollins
Lisa
L
Goltsova
Tatiana
T
Chen
Si-Yi
SY
Huang
Xue F
XF
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D018946:Chemokine CCL5 / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology
D019496:Cancer Vaccines; D018946:Chemokine CCL5; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin