Bystander effect of antitumour therapy

Abstract

This application comes from one of the leading groups developing clinical applications for gene therapy at the US National Institutes of Health. The invention involves the use of genetically modified mouse fibroblast cells to deliver a defective retrovirus at high titre to cells within a tumour or body cavity. This retrovirus carries a non-mammalian gene encoding a prodrugactivating enzyme so that transduced target cells are made sensitive to the cytotoxic effects of an otherwise harmless prodrug (gancyclovir for the herpes simplex thymidine kinase gene, for instance). Since the retrovirus-producing cells carry the same prodrug activating (suicide) gene they can be destroyed after the therapeutic gene transfer has been achieved. The application demonstrates that gene transfer into all target cells is not required in order to produce complete tumour regression on exposure to the cytotoxic prodrug due to bystander effects on untransduced cells.