Cellular immunity induced by a recombinant adenovirus- human dendritic cell vaccine for melanoma
Open Access
- 1 January 2013
- journal article
- Published by BMJ in Journal for ImmunoTherapy of Cancer
- Vol. 1 (1), 19
- https://doi.org/10.1186/2051-1426-1-19
Abstract
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. 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. 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. 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.This publication has 39 references indexed in Scilit:
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