Nature Medicine 11, 1073 - 1081 (2005)
Published online: 18 September 2005; | doi:10.1038/nm1297
Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cellsCaroline Cole1, 2, 5, Jian Qiao1, 5, Timothy Kottke1, Rosa Maria Diaz1, Atique Ahmed1, Luis Sanchez-Perez1, 2, Gregory Brunn3, Jill Thompson1, John Chester4
& Richard G Vile1, 21
Molecular Medicine Program, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, USA. 2
Department of Immunology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, USA. 3
Department of Transplantation Biology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, USA. 4
Division of Cancer Medicine Research, Cancer Research UK Clinical Centre, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK. 5
These authors contributed equally to this work.
Correspondence should be addressed to Richard G Vile vile.richard@mayo.edu Antigen-specific T cells circulate freely and accumulate specifically at sites of antigen expression. To enhance the survival and targeting of systemically delivered viral vectors, we exploited the observation that retroviral particles adhere nonspecifically, or 'hitchhike,' to the surface of T cells. Adoptive transfer of antigen-specific T cells, loaded with viruses encoding interleukin (IL)-12 or Herpes Simplex Virus thymidine kinase (HSVtk), cured established metastatic disease where adoptive T-cell transfer alone was not effective. Productive hand off correlated with local heparanase expression either from malignant tumor cells and/or as a result of T-cell activation by antigen, providing high levels of selectivity for viral transfer to metastatic tumors in vivo. Protection, concentration and targeting of viruses by adsorption to cell carriers represent a new technique for systemic delivery of vectors, in fully immunocompetent hosts, for a variety of diseases in which delivery of genes may be therapeutically beneficial.
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