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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Cole, C; Qiao, J; Kottke, T; Diaz, RM; Ahmed, A; Sanchez-Perez, L; Brunn, G; Thompson, J; Chester, J; Vile, RG

Published Date

  • October 2005

Published In

Volume / Issue

  • 11 / 10

Start / End Page

  • 1073 - 1081

PubMed ID

  • 16170322

Pubmed Central ID

  • 16170322

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm1297

Language

  • eng

Conference Location

  • United States