The perforin-dependent immunological synapse allows T-cell activation-dependent tumor targeting by MLV vector particles

T. Kottke, J. Qiao, R. M. Diaz, A. Ahmed, B. Vroman, J. Thompson, L. Sanchez-Perez, Richard Geoffrey Vile

Research output: Contribution to journalArticle

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Abstract

We have reported that retroviral particles adhered to the surface of antigen-specific T cells can be carried to metastases following adoptive transfer in vivo, a process we have called viral hitch hiking. Following antigen-driven T-cell accumulation at tumors, viral particles productively infect tumor cells via envelope/receptor dependent interactions ('hand on' of virus from the T cell to the tumor cell). We describe here a second envelope/receptor independent pathway of viral hand on from T cells, dependent on T-cell activation. We show that the endosomolytic property of perforin promotes release of viral particles from endosomes into which they are co-delivered along with cytotoxic granules from the activated T cell. Therefore, hand on of MLV particles lacking any envelope can be used for in vivo delivery of vectors, where targeting is at the extremely specific level of recognition of antigen by the T-cell receptor, thereby dispensing with the need to engineer viral envelopes. These data reveal a novel pathway by which MLV viral particles exploit a functiol immunological synapse and present new opportunities both to improve the efficacy of adoptive T-cell transfer and to target vectors for systemic gene delivery.

Original languageEnglish (US)
Pages (from-to)1166-1177
Number of pages12
JournalGene Therapy
Volume13
Issue number15
DOIs
StatePublished - Aug 2006

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Immunological Synapses
Perforin
T-Lymphocytes
Neoplasms
Virion
Adoptive Transfer
Hand
Endosomes
Surface Antigens
T-Cell Antigen Receptor
Neoplasm Metastasis
Viruses
Antigens

ASJC Scopus subject areas

  • Genetics

Cite this

The perforin-dependent immunological synapse allows T-cell activation-dependent tumor targeting by MLV vector particles. / Kottke, T.; Qiao, J.; Diaz, R. M.; Ahmed, A.; Vroman, B.; Thompson, J.; Sanchez-Perez, L.; Vile, Richard Geoffrey.

In: Gene Therapy, Vol. 13, No. 15, 08.2006, p. 1166-1177.

Research output: Contribution to journalArticle

Kottke, T, Qiao, J, Diaz, RM, Ahmed, A, Vroman, B, Thompson, J, Sanchez-Perez, L & Vile, RG 2006, 'The perforin-dependent immunological synapse allows T-cell activation-dependent tumor targeting by MLV vector particles', Gene Therapy, vol. 13, no. 15, pp. 1166-1177. https://doi.org/10.1038/sj.gt.3302722
Kottke, T. ; Qiao, J. ; Diaz, R. M. ; Ahmed, A. ; Vroman, B. ; Thompson, J. ; Sanchez-Perez, L. ; Vile, Richard Geoffrey. / The perforin-dependent immunological synapse allows T-cell activation-dependent tumor targeting by MLV vector particles. In: Gene Therapy. 2006 ; Vol. 13, No. 15. pp. 1166-1177.
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