Short-term neuropathological aspects of in vivo suicide gene transfer to the F98 rat glioblastoma using liposomal and viral vectors

To date, only few preclinical protocols on liposomal suicide gene transfer in tumors have been published, none of which directly compared viral to lip osomal vectors in terms of immunoreactivity and efficacy. We thus studied t he neuropathological alterations in 80 rats being treated for glioblastoma using liposomal and, for comparison, adenoviral and retroviral suicide gene transfer approaches to identify vector-associated efficacy and toxicity fo r further clinical studies. 62 rats served as controls. F98 tumors were est ablished in Fisher rats and transfected in vivo with the thymidine kinase g ene of herpes simplex virus (HSVtk) by a single intratumoral application an d an implanted intratumoral continuous delivery system. Three days later ga nciclovir was given intraperitoneally for 14 days. The animals were sacrifi ced 17 days post completed gene transfer. Brains were examined histological ly and immunohistochemically using markers for immunocompetent cells. Ten a nimals showed complete tumor regression; they all belonged to the liposomal and adenoviral groups. In 6 of 10 experimental groups considerable numbers of lymphocytes along the margins of the regression cavities could be obser ved. Control animals of the liposomal and, adenoviral groups showed only li ttle lymphocytic infiltration, underlining the minimal immunogenicity of th ese carriers. In contrast, the retroviral control group featured a high lym phocyte infiltration. In summary, this study indicates that, in terms of bo th efficacy and immunoreaction, liposomes are as appropriate as adenoviruse s in the treatment of rat glial tumors using suicide gene transfer strategi es.