Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intratracheal gene therapy reduction of irradiation-induced inflammatory cytokines does not protect orthotopic Lewis lung carcinomas

In Vivo. 2003 Jan-Feb;17(1):13-21.

Abstract

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 intrapulmonary MnSOD-PL gene therapy in lung cancer patients for protection of normal lung tissue from irradiation while allowing effective irradiation-mediated tumor control.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / therapy*
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cell Survival / radiation effects
  • Female
  • Gene Expression
  • Genetic Therapy / methods*
  • Infusion Pumps
  • Interleukin-1 / genetics
  • Interleukin-1 / pharmacology
  • Liposomes
  • Lung / immunology
  • Lung / radiation effects
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Plasmids
  • RNA, Messenger / analysis
  • Radiation Pneumonitis / immunology
  • Radiation Pneumonitis / therapy*
  • Radiation, Ionizing
  • Superoxide Dismutase / genetics*
  • Trachea
  • Transforming Growth Factor alpha / genetics
  • Transforming Growth Factor alpha / pharmacology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured

Substances

  • Interleukin-1
  • Liposomes
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta
  • Superoxide Dismutase