Journal for ImmunoTherapy of Cancer | |
Cellular immunity induced by a recombinant adenovirus- human dendritic cell vaccine for melanoma | |
Lisa H Butterfield2  Lazar Vujanovic1  Hadas Prag Naveh1  | |
[1] Department of Medicine, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213, USA;University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213, USA | |
关键词: Cancer vaccines; Cytokines; T cells; Dendritic cells; Adenovirus; | |
Others : 814906 DOI : 10.1186/2051-1426-1-19 |
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received in 2013-06-25, accepted in 2013-11-13, 发布年份 2013 | |
【 摘 要 】
Background
Human Adenoviral vectors (HAdV) are immunogenic vectors which have been tested in many vaccination and gene therapy settings. Dendritic cells (DC) transduced by genetically engineered HAdV-5 (HAdV-5/DC), are investigational cancer vaccines being tested clinically. We have previously examined immune responses to HAdV-5 -encoded melanoma tumor antigens. Here, we determined whether the HAdV-5/DC also present immunogenic HAdV-5 vector-derived antigens, and characterized the cellular immune response to the viral as well as encoded melanoma tumor antigens.
Methods
Both CD4+ and CD8+ HAdV-5-specific T cell responses were examined in vitro, with cells from both 8 healthy donors (HD) and 2 melanoma patients. PBMC were stimulated weekly with HAdV-5/DC and responses were examined after each stimulation. We also tested HAdV-5 neutralizing antibody levels and natural killer (NK) cell and regulatory T cell (Treg) activation and expansion in vitro.
Results
HAdV-5/DC rapidly induced a high frequency of type 1 cytokine producing HAdV-5-specific CD8+ and CD4+ T cells. IFNγ and TNFα-producing T cells predominate. Those with pre-existing cellular memory to HAdV-5 had more robust responses to the HAdV-5 as well as tumor-associated antigens. NK cells are activated while Treg are only minimally and transiently expanded.
Conclusions
This study demonstrates that HAdV-5/DC promote strong type I cellular immunity to viral vector-derived antigens as well as to the encoded tumor antigens. The cytokine and chemokine milieu produced by HAdV-5/DC and the activated HAdV-5-specific T cells may enhance responses to encoded tumor antigens as well. These properties make HAdV-5/DC a cancer vaccine capable of activating type 1 virus and tumor antigen-specific immunity in a cooperative way.
【 授权许可】
2013 Naveh et al.; licensee BioMed Central Ltd.
【 预 览 】
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Figure 1. | 56KB | Image | download |
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