Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells

Caroline Cole, Jian Qiao, Timothy Kottke, Rosa Maria Diaz, Atique Ahmed, Luis Sanchez-Perez, Gregory Brunn, Jill Thompson, John Chester, Richard G. Vile*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1073-1081
Number of pages9
JournalNature Medicine
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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