274. Combination of a Second Generation Genetically Modified Herpes Simplex Virus 1 (HSV 1) with Paclitaxel in the Treatment of Breast Cancer In Vitro

Background A genetically modified HSV1, JS1/ICP34.5-/ICP47-, incorporating the hGM-CSF transgene and which selectively replicates and kills tumour cells, is being tested in a Phase I clinical trial in a number of solid tumours. The preliminary results are encouraging and planning for a Phase II clinical trial in combination with chemotherapy in breast cancer is underway. Tumour selectivity is conferred by the deletion of ICP34.5, which is also an anti-apoptotic gene. Deletion of ICP47, which blocks antigen presentation, and the insertion of GM-CSF aims to enhance the immune response to infected malignant cells. The aim of the in vitro work was to assess the effects of combining the virus and paclitaxel in breast cancer cell lines and to study the mechanism of action of the virus, paclitaxel and the combination of the two.