Recombinant adenovirus has been used in gene transfer applications, including cancer immunotherapy and infectious disease. Immunity to the adenoviral vector is known to include a potent humoral response; however, the cellular response is poorly characterized. Here, we evaluated the virus-specific response to an AdV encoding three melanoma tumor antigens (Tyrosinase, MART-1 and MAGE-A6 (AdVTMM2)) in healthy donors and patients with melanoma. CD4+ and CD8+ T cell responses were followed weekly by multi-cytokine ELISPOT assays (IFN-gamma, IL-2, IL-10 and TNF) and flow cytometric analysis in vitro. NK cells and Treg were also assessed. We found a strong type 1-skewed response with INFg secreted by CD4+ cells beginning within 7 days of stimulation and carrying through 3 weekly stimulations. Strong type 1 CD8+ T cell immunity was also detected to the virus. Treg increased transiently and an activated, INFg-producing subset of NK cells became evident. Melanoma patient cells also show a type-1 CD8+ T cell and CD4+ T cell response to the adenovirus. While strong, these virus-specific responses did not mask responses to the melanoma antigens. Melanoma patients vaccinated with the engineered DC vaccine in a new clinical trial respond immunologically to both the viral vector and encoded melanoma antigens, and show modulation of NK cells and Treg post-vaccination. Therefore, AdV-engineered DC promote a strong type 1 virus- and melanoma antigen-specific response, in vitro and in vivo.
- Copyright © 2013 by The American Association of Immunologists, Inc.