Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection Journal Article


Authors: Miller, G.; Lahrs, S.; Pillarisetty, V. G.; Shah, A. B.; DeMatteo, R. P.
Article Title: Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection
Abstract: Dendritic cells (DCs) are potent antigen-presenting cells with the potential for cancer immunotherapy. Adenoviral-mediated gene transfer is an attractive means to manipulate the immunostimulatory properties of DCs for therapeutic advantage. Because adenovirus induces DC maturation, we postulated that it would significantly alter their immune functions. Infected DCs markedly increased allogeneic and antigen-specific T-cell proliferation, and augmented natural killer cell lytic activity and IFN-γ production. The enhanced effector cell stimulation by infected DCs was dependent on their secretion of interleukin 12. Immunization with infected DCs pulsed with tumor antigen protected against flank tumors in 78% of mice and induced a memory response. Antitumor immunity was dependent on both T cells and natural killer cells. Antigen-pulsed, mock-infected DCs were nonprotective. The findings that adenoviral vectors alone critically alter DC immune functions and antitumor properties have important implications for the design and interpretation of immunotherapy regimens using vector-based gene transfer to modulate immunity.
Keywords: controlled study; nonhuman; lymphocyte proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; cancer immunotherapy; dendritic cell; animal experiment; animal model; tumor antigen; mice, inbred c57bl; lymphocyte activation; dendritic cells; chemotaxis; antigens, neoplasm; gamma interferon; lymphoma; gene therapy; beta galactosidase; natural killer cell; killer cells, natural; tumor immunity; cytokine production; cytolysis; immunostimulation; virus infection; cytokine release; immunotherapy, adoptive; interleukin 12; adenoviridae; virus vector; coculture techniques; immunological memory; adenovirus; interleukin-12; interferon type ii; ovalbumin; male; priority journal; article
Journal Title: Cancer Research
Volume: 62
Issue: 18
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2002-09-15
Start Page: 5260
End Page: 5266
Language: English
PUBMED: 12234994
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus