Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intratracheal gene therapy reduction of irradiation-induced inflammatory cytokines does not protect orthotopic Lewis lung carcinomas
Guo, H.; Epperly, M.W.; Bernarding, M.; Nie, S.; Gretton, J.; Jefferson, M.; Greenberger, J.S.
In Vivo 17(1): 13-21
2003
ISSN/ISBN: 0258-851X PMID: 12655784 Document Number: 566136
Background: Intratracheal injection of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prior to single fraction or fractionated irradiation of C57BL/6J mouse lung has been demonstrated to protect the lung from irradiation-induced damage. Materials and Methods: To determine whether irradiation-induced inflammatory cytokine levels influenced the recovery of tumors following single fraction irradiation, mice with orthotopic Lewis Lung Carcinoma (3LL) tumors received MnSOD-PL treatment 24 hours after tumor implantation and 24 hours prior to irradiation. Subgroups were implanted with Alzet pumps continuously replacing levels of inflammatory cytokines over 7 days. Results: In cytokine-treated mice, there was no detectable significant alteration in radiotherapy-mediated improved survival (tumor regrowth delay) compared to irradiated control mice. Each group of mice that received MnSOD-PL had increased survival compared to irradiated controls. Conclusion: These results support the anticipated safety of intrapulmonamy MnSOD-PL gene therapy in lung cancer patients for protection of normal lung tissue from irradiation while allowing effective irradiation-mediated tumor control.