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

Cole, C., Qiao, J., Kottke, T., Diaz, R. M., Ahmed, A., Sanchez-Perez, L., Brunn, G., Thompson, J., Chester, John D. ORCID: https://orcid.org/0000-0002-7830-3840 and Vile, R. G. 2005. Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. Nature Medicine 11 (10) , pp. 1073-1081. 10.1038/nm1297

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Publisher:	Nature Publishing Group
ISSN:	1078-8956
Last Modified:	19 Oct 2022 08:42
URI:	https://orca.cardiff.ac.uk/id/eprint/18803

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