Jehad Zweiri
University of Liverpool-Medical School, UK
Title: Demonstration of bystander killing with GCV-preloaded HSV-TK gene modified tumour cells: An improvement for cancer therapeutic
Biography
Biography: Jehad Zweiri
Abstract
It is well established that GCV causes bone-marrow toxicity in CMV-infected patients, particularly on the neutrophil lineage. Therefore it may also induce T cell immunosuppression, although this does not appear to have been directly investigated. If GCV does have such a side-effect it may reduce the efficiency of the immunological component of the bystander effect induced by HSV-TK/GCV. The rationale for the studies described here was to devise a strategy whereby the TK+ve tumour cells would be exposed to GCV in vitro, in order to pre-load the tumour cells with GCV, wash the excess GCV away and then inject the cells for study of their in vivo bystander effect. It is also possible that the intravenous administration of GCV does not allow the achievement of a therapeutically high enough dose at the site of injection of TK+ve cells (e.g. in the peritoneum). By contrast, the pre-loading of the TK+ve tumour cells with GCV may ensure that the cells have received the required dose of GCV. This may reduce the possible immuno toxic effects of GCV. This in turn may enhance the systemic immune mediated anti-tumour efficacy of treatment with HSV-TK expressing tumour cells.