Local tumor irradiation augments the antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model

Cancer Gene Therapy
Katalin LumniczkyGeza Safrany

Abstract

The combined therapeutic effect of cytokine-producing cancer cell vaccines and local radiotherapy was studied in a mouse glioma 261 (GI261) brain tumor model. Brain tumor-bearing mice were treated with cytokine (IL -4, IL-6, IL-7, GM-CSF, TNF-alpha, LIF, LT) producing vaccines made by in vitro transduction of GI261 cells with the corresponding adenoviral vectors. Vaccines producing either IL-4 or GM-CSF cured 20-40% of mice. The antitumor effect strongly depended on the secreted cytokine level. Vaccination therapy induced specific activation of cytotoxic T lymphocytes measured by cell-mediated cytotoxicity assay. Brain tumors were heavily infiltrated by CD4+ lymphocytes after treatment with IL-4- or GM-CSF-secreting cells. GM-CSF vaccination induced moderate CD8+ infiltration, as well. Depleting either CD4+ or CD8+ lymphocyte subsets abolished the anticancer effect of GM-CSF-expressing cells. Strong synergism was observed by combining cytokine vaccination (GM-CSF, IL-4, IL-12) with local tumor irradiation: about 80-100% of the glioma-bearing mice was cured. The high efficiency of combined treatment was maintained even under suboptimal conditions when neither of the modalities cured any of the mice alone. This suggests that vacc...Continue Reading

References

Jul 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·E NakayamaL J Old
May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·T AokiT Honjo
Dec 1, 1989·Journal of Neurosurgery·M S MahaleyB B Peace
Jan 1, 1997·Advances in Pharmacology·D L ShawlerR E Sobol
Mar 10, 1999·Journal of the National Cancer Institute·M SalehA H Kaye
Apr 9, 1999·Cancer Gene Therapy·B BadieD A Boothman
Dec 10, 1999·Journal of Neurosurgery·W C BroaddusH L Fillmore
Mar 4, 2000·Journal of Neurosurgery·F DiMecoA Olivi
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·F GriscelliP Yeh
Sep 12, 2000·Journal of Neuro-oncology·A NatsumeJ Yoshida
Feb 24, 2001·Journal of Immunotherapy·B ChenI Fodor
Jan 5, 2002·Advances in Experimental Medicine and Biology·S DesaknaiG Safrany

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Citations

Jun 27, 2006·Pathology Oncology Research : POR·Katalin Lumniczky, Géza Sáfrány
Oct 20, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Andrea BaloghKatalin Lumniczky
Jul 27, 2007·Clinical & Experimental Metastasis·Hiroshi YokouchiTakashi Nishimura
Mar 24, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Patricia L Robertson
May 10, 2003·Brain Research. Brain Research Reviews·Paul R WalkerPierre Yves Dietrich
Oct 19, 2005·Gene Therapy·P GalloP Monaci
Apr 28, 2005·International Journal of Cancer. Journal International Du Cancer·Yuxia MengJean-Yves Delattre
Sep 12, 2009·Brain Pathology·Stefaan Van GoolSteven De Vleeschouwer
Oct 18, 2006·International Journal of Cancer. Journal International Du Cancer·Karin E SmithAnna Darabi
Jan 18, 2006·International Journal of Radiation Oncology, Biology, Physics·Michael R HorsmanJolyon H Hendry
Oct 4, 2005·International Journal of Radiation Oncology, Biology, Physics·Sandra DemariaSilvia C Formenti
Oct 4, 2005·Neurological Research·Christian W Sikorski, Maciej S Lesniak
Mar 26, 2010·Radiation Research·Bertil R R PerssonLeif G Salford
Jul 10, 2014·Journal of Cancer Research and Clinical Oncology·Wei ZhouZhenyu Shao
Sep 3, 2005·Cancer Gene Therapy·S E LawlerE A Chiocca
Aug 11, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elizabeth W NewcombSilvia C Formenti

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