Research in my laboratory is focused on the molecular biology of adenoviruses and the development of viral vectors for gene transfer and gene therapy. Transducing vectors based on adenoviruses are fast becoming the single most important mammalian cell expression system and we have developed and continue to refine much of the technology for construction and use of adenovirus vectors. Ad vectors can be used as research tools for studying protein expression and function in mammalian cells, as recombinant viral vaccines, and in gene therapy, and my lab has worked on all of these aspects. A major current interest is the development of Ad vectors for immunotherapy of cancer. We have constructed several vectors expressing cytokines that regulate immune responses to tumour cells and are studying how these vectors can stimulate an anti tumour response in murine models of cancer and in human malignancy. We are also developing Ad vectors, and refining vector technology, for therapy of genetic diseases.
Parks, R. J., Chen, L., Anton, M., Sankar, U., Rudnicki, M. A. and Graham, F. L. A new helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc. Natl. Acad. Sci. U.S. 93: 13565-13570, 1996.
Bramson, J., Hitt, M., Addison, C.L., Mulder, W. J., Gauldie, J. and Graham, F. L. Direct intratumoral injection of an adenovirus expressing IL-12 induces regression and long- lasting immunity which is associated with highly localized expression of IL-12. Human Gene Therapy 7: 1995-2002, 1996.
Anton, M. and Graham, F. L. Site-specific recombination mediated by an adenovirus vector expressing the Cre recombinase protein: a molecular switch for control of gene expression. J. Virol. 69:4600-4606, 1995.
Addison, C. A., Braciak, T., Ralston, R., Muller, W. J., Gauldie, J. and Graham, F. L. Intratumoural injection of an adenovirus expressing interleukin-2 induces tumour regression and long term immunity in a murine breast cancer model. Proc. Natl. Acad. Sci. US. 92: 8522-8526, 1995.
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