Cellular immunity delimits adenoviral gene therapy strategies for the treatment of neoplastic diseases

Background: Adenoviral gene therapy is a promising new approach for the tre atment of neoplastic diseases. To design rational clinical trials and disti nguish the effects of therapeutic transgene expression From those caused by viral infection alone, the immune response to the vector must be understoo d. In these experiments, we further define cellular immunity to recombinant adenovirus. Methods: The immune response to hepatic adenoviral gene transfer was studie d in infected mice by depleting T cells with an anti-CD3 antibody, measurin g splenocyte cytokine production, determining the impact of transgene expre ssion on inflammation, and assessing Liver MHC protein expression. Results: The cellular immune response to recombinant adenovirus is (I) aver ted by T lymphocyte depletion, (2) marked by a T(H)1 response with increase d IL-2 production, (3) directed against both the transgene product and vira l proteins, and (4) associated with increased hepatocyte MHC Class I expres sion. Conclusions: It is necessary to take into consideration the constraints imp osed by the immunogenicity of recombinant adenovirus and its transient tran sgene expression in the clinical application of adenoviral gene transfer fo r the treatment of cancer.