Access

Article

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 cells

Caroline 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 Vile1,2

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.

$rb.Type.Code