643. Enhanced Distribution of LCMV-Pesudotyped Bicistronic Lentiviral Vector Containing a Recombinant HSV-TK and EGFRwt for Glioblastoma Treatment

Abstract

Introduction: •Malignant gliomas, the largest group of primary intracerebral tumours, are one of the most difficult-to-cure cancers. The outcome has not improved significantly in the past years, despite considerable advances in our understanding of the molecular pathogenesis and the improvement of surgical techniques, radio- and chemotherapy. For glioblastoma multiforme (GBM), the most malignant form of glioma, the median survival time is generally less than one year.•Invasive glioma cells escape current therapies and are initiating recurrent tumors. Although complete remission of experimental GBM on MRI was observed, recurrent tumors came up which were frequently observed at different sites compared to the primary tumor 1. Thus invasive cells migrated to thes areas and initiated recurrent tumors.•The distribution of the therapeutic gene needs to be enhanced in order to target the invasive glioma cells and thereby improve the therapeutic effect and prolong the recurrence-free time window.By introducing EGFR, a gene that enhances invasion2, in addition to the suicide gene HSV-tk into our vector system, we want to improve the distribution of the therapeutic gene and also track invasive tumor cells.Key findings: •Expression of EGFR initiates an invasive program in transduced glioblastoma cells in vitro.•EGFR mediated infiltration of glioblastoma cells is retained in vivo in a rat xenograft model. [figure3 a &b]•The bicistronic lentiviral vector containing HSV-TK and EGFR [figure4] shows satisfactory cytotoxic profile in vitro. [figure5a & b] View Large Image | Download PowerPoint SlideConclusion: Expression of EGFR can enhance infiltrative nature of glioblastoma cells both in vitro and in vivo. We are currently taking preparations for an in vivo therapeutic study of our bicistronic lentiviral construct containing a recombinant HSV-TK and EGFR in a clinically relevant GBM rat model.