Background and Objectives : The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is an attenuated virus originally produced as a viral vaccine, but it also serves as an efficient gene transfer vehicle. The main goals of
this
study were to examine determinants of gene transfer using DISC vectors for squamous cell carcinoma and to evaluate the efficacy of vaccination with the DISC virus carrying a combination of immunomodulatory genes (IL-2, GM-CSF) as cancer therapy
in
a
model of squamous cell cancer in the C3H/HeJ mice. Materials and Methods : We determinated the gene and protein expression of DISC-IL-2 and DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also, we evaluated the ex vivo vaccination
effects of DISC-IL-2 and DISC-GMCSF on preventing the development of SCCVII tumor. Results : SCCVII cells transduced by the DISC virus vector (MOI=10) carrying the IL-2, or the GM-CSF gene, produced nanogram quantities of IL-2 or GM-CSF per
106 cells. Of particular interest was the observation that cells irradiated at different doses (5,000 cGy, 10,000 cGy) secreted levels of GM-CSF or IL-2 that were comparable to non-irradiated cells. In vivo vaccination using tumor
cells
transduced ex vivo with DISC-IL-2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (p<0.01). Among the multiple immunomodulatory transgenes vaccination groups, the DISC-GMCSF transfected vaccine showed the greatest
suppression of
tumor development and growth (p<0.001). Conclusion : These data demonstrate that ; 1) The DISC virus vector is capable of efficient gene transfer to SCCVII cells, 2) The GM-CSF secreting, genetically modified tumor vaccine (SCCVII/GMCSF)
efficiently
protected against tumor cell challenge and suppressed tumor growth in our tumor model. The DISC virus-mediated, cytokine gene transfer may prove to be useful in clinical therapy for head and neck cancers.
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