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

Research output: Contribution to journalArticle

87 Citations (Scopus)

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

Fingerprint

T-cells
Tumors
Viruses
T-Lymphocytes
Antigens
Adoptive Transfer
Neoplasms
CD27 Antigens
Thymidine Kinase
Simplexvirus
Therapeutics
Interleukin-12
Adsorption
Hand
Genes
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cole, C., Qiao, J., Kottke, T., Diaz, R. M., Ahmed, A., Sanchez-Perez, L., ... Vile, R. G. (2005). Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. Nature Medicine, 11(10), 1073-1081. https://doi.org/10.1038/nm1297

Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. / Cole, Caroline; Qiao, Jian; Kottke, Timothy; Diaz, Rosa Maria; Ahmed, Atique; Sanchez-Perez, Luis; Brunn, Gregory; Thompson, Jill; Chester, John; Vile, Richard G.

In: Nature Medicine, Vol. 11, No. 10, 01.10.2005, p. 1073-1081.

Research output: Contribution to journalArticle

Cole, C, Qiao, J, Kottke, T, Diaz, RM, Ahmed, A, Sanchez-Perez, L, Brunn, G, Thompson, J, Chester, J & Vile, RG 2005, 'Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells', Nature Medicine, vol. 11, no. 10, pp. 1073-1081. https://doi.org/10.1038/nm1297
Cole, Caroline ; Qiao, Jian ; Kottke, Timothy ; Diaz, Rosa Maria ; Ahmed, Atique ; Sanchez-Perez, Luis ; Brunn, Gregory ; Thompson, Jill ; Chester, John ; Vile, Richard G. / Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. In: Nature Medicine. 2005 ; Vol. 11, No. 10. pp. 1073-1081.
@article{cbb4fba16ac44ca8993db1e110578596,
title = "Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells",
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.",
author = "Caroline Cole and Jian Qiao and Timothy Kottke and Diaz, {Rosa Maria} and Atique Ahmed and Luis Sanchez-Perez and Gregory Brunn and Jill Thompson and John Chester and Vile, {Richard G.}",
year = "2005",
month = "10",
day = "1",
doi = "10.1038/nm1297",
language = "English (US)",
volume = "11",
pages = "1073--1081",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells

AU - Cole, Caroline

AU - Qiao, Jian

AU - Kottke, Timothy

AU - Diaz, Rosa Maria

AU - Ahmed, Atique

AU - Sanchez-Perez, Luis

AU - Brunn, Gregory

AU - Thompson, Jill

AU - Chester, John

AU - Vile, Richard G.

PY - 2005/10/1

Y1 - 2005/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=27144483926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27144483926&partnerID=8YFLogxK

U2 - 10.1038/nm1297

DO - 10.1038/nm1297

M3 - Article

C2 - 16170322

AN - SCOPUS:27144483926

VL - 11

SP - 1073

EP - 1081

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 10

ER -