HSVtkHerpes Simplex Virus Thymidine Kinase
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HSVtk conferred sensitivity to GCV to ~81 per cent PLTK41.1 cells when treated with 3 [micro]g/ml GCV for 3 days, while the cell kill was enhanced to 91 per cent when PLTK41.1 cells were incubated for 6 days at same concentration (Fig.
HSVtk, the enzyme used in prodrug activation, has been introduced into the tumour via retroviral vectors, by directly injecting VPC into the tumours.
Simultaneous expression of HSVtk and IL-2 was shown to potentiate the induction of an immune response (28).
In the present study we used a combination strategy with prodrug activation, for which we have constructed a retrovirus producing cell line pLTK41.1 carrying HSVtk, and immunotherapy using plasmid IL-2 DNA.
Our experimental approach provides an opportunity to have insight into the role of IL-2 and HSVtk in exclusively inducing the secondary target immune cells viz., NK, DCs (the primary target being T cells).
Generation of an anti-tumour immune response in a non-immunogenic tumour: HSVtk killing in vivo stimulates a mononuclear cell infiltrate and a Th1-like profile of intratumoural cytokine expression.