Host Immune Responses to Recombinant Adenoviral Vectors
Johanne M. Kaplan
Recombinant adenoviruses (Ad) are versatile gene delivery vectors capable of infecting a broad range of cell types without a requirement for cell division. They are being developed for a variety of clinical applications such as correction of inherited disorders, cancer gene therapy and treatment of cardiovascular disease. However, results from animal studies suggest that the clinical usefulness of Ad vectors may be limited by their immunogenicity. Neutralizing antibodies elicited by input virus particles interfere with vector readministration which is expected to be necessary for applications such as chronic treatment of genetic disorders. In addition, the induction of cytotoxic T lymphocytes (CTLs) directed against adenoviral proteins and, more importantly, immunogenic transgene products expressed by transfected cells typically results in limited persistence of transgene expression. To address these issues, several approaches are being developed to inhibit or circumvent host humoral and cellular immune responses and improve the therapeutic potential of Ad vectors.