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Cellular immunity induced by a recombinant adenovirus-human dendritic cell vaccine for melanoma

Naveh, HP and Vujanovic, L and Butterfield, LH (2013) Cellular immunity induced by a recombinant adenovirus-human dendritic cell vaccine for melanoma. Journal for ImmunoTherapy of Cancer, 1.

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Abstract

© 2013 Naveh et al. 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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Naveh, HP
Vujanovic, Llnvst3@pitt.eduLNVST3
Butterfield, LHlhb3@pitt.eduLHB3
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 1 January 2013
Date Type: Publication
Journal or Publication Title: Journal for ImmunoTherapy of Cancer
Volume: 1
DOI or Unique Handle: 10.1186/2051-1426-1-19
Schools and Programs: School of Medicine > Immunology
School of Medicine > Medicine
School of Medicine > Surgery
Refereed: Yes
Date Deposited: 02 Dec 2016 18:25
Last Modified: 16 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29641

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