Local and systemic antitumor response after combined therapy of mouse metastatic tumors with tumor cells expressing IFN-alpha and HSVtk: perspectives for the generation of cancer vaccines

Gene Therapy
L SantodonatoM Ferrantini

Abstract

In this study, we have evaluated the local versus systemic antitumor response in tumor-bearing mice subjected to a combined therapeutic regimen based on the injection of genetically modified Friend erythroleukemia cells (FLC) producing IFN-alpha and expressing the HSVtk (tk) gene, and we have investigated the host immune mechanisms involved in tumor rejection and development of antitumor immunity. Repeated subcutaneous (s.c.) injections of IFNtk-expressing tumor cells, followed by GCV administration, were effective in counteracting the growth of both contralateral parental tumors as well as visceral metastases, whereas similar treatments with control tk cells (i.e. nonproducing IFN) were ineffective. Morphologic analyses of the homolateral and contralateral tumor tissues and in vivo immunosuppression experiments with specific monoclonal antibodies revealed that both CD4+ and CD8+ T lymphocytes played essential roles in the generation of a definite antitumor response after the combined therapeutic regimen. We have also compared the effectiveness of irradiated versus viable tumor vaccines co-expressing the two genes in the FLC model and in the poorly immunogenic metastasizing TS/A adenocarcinoma tumor system. Repeated injections ...Continue Reading

Citations

Dec 18, 2001·International Journal of Cancer. Journal International Du Cancer·B M ChenS R Roffler
Mar 20, 2002·Cytokine & Growth Factor Reviews·Filippo BelardelliJohn M Kirkwood
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·H M HortonS E Parker
May 29, 2007·Biochimie·Maria FerrantiniFilippo Belardelli
May 29, 2002·Cancer Gene Therapy·C CherbonnierF Hirsch
May 18, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·L M AkyürekE G Nabel

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