AV.TK-mediated killing of subcutaneous tumors in situ results in effectiveimmunization against established secondary intracranial tumor deposits

Gene transfer vectors expressing herpes simplex thymidine kinase (HSVtk), i n addition to direct killing of tumor cells, often have an associated local 'bystander effect' mediated by metabolic coupling of tumor cells. A system ic antitumor effect mediated by the immune system, termed the distant bysta nder effect, has also been reported. We have observed the development of cy totoxic T-lymphocyte (CTL) populations and long-lasting antitumor immunity following treatment of subcutaneous tumors with an adenoviral vector expres sing HSVtk (AV.TK) and ganciclovir (GCV) in rat glioma model. This vaccinat ion effect seen with AV.TK/GCV treatment of subcutaneous tumor could even a brogate or retard growth of previously established secondary intracranial t umors.