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Radiation Protection by MnSOD-Plasmid Liposome Gene Therapy

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Oxidative Stress in Cancer Biology and Therapy

Abstract

Understanding the molecular mechanism of ionizing irradiation killing of normal tissues compared to tumor cells has uncovered potential therapeutic strategies for radiotherapeutic dose escalation in the treatment of solid tumors. One strategy exploits the difference in redox balance between normal tissues and solid tumors with organ-specific and systemic (intravenous) administration of plasmid liposomes containing the human manganese superoxide dismutase (MnSOD) transgene. When delivered, this transgene product produced significant protection against single fraction and fractionated radiation in organ-specific radioprotective gene therapy by each of several routes of administration (inhalation, swallowed, intravesicle, intra-intestinal), and this strategy was shown to avoid tumor tissue. Furthermore, systemic administration of MnSOD-PL also provides radioprotection with selective normal tissue reduction of apoptosis compared to tumor. The complex mechanism of selective normal tissue protection involves specific differences in redox balance, constitutive MnSOD expression, and compensatory metabolic changes, many of which can enhance the therapeutic effect.

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Acknowledgment

Supported by NIAID/NIH Research Grant U19A1068021

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Joel S. Greenberger MD & Michael W. Epperly PhD

  2. Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA

    Valerian E. Cagan PhD

  3. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA

    James Peterson PhD

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  1. Joel S. Greenberger MD
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  2. Valerian E. Cagan PhD
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  3. James Peterson PhD
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  4. Michael W. Epperly PhD
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Correspondence to Joel S. Greenberger MD .

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Editors and Affiliations

  1. Free Radical & Radiation Biology, Graduate Program, University of Iowa, Iowa City, 52242, Iowa, USA

    Douglas R. Spitz

  2. Duluth Clinic, Radiation Oncology, University of Minnesota, East 3rd Street 400, Duluth, 55805, Minnesota, USA

    Kenneth J. Dornfeld

  3. James H. Quillen College of Medicine, Internal Medicine, East Tennessee State University, Johnson City, 37614, Tennessee, USA

    Koyamangalath Krishnan

  4. Radiation Oncology, Cancer Biology and Pediatrics, Vanderbilt Medical School, 21st Ave. 1161, Nashville, 37232, Tennessee, USA

    David Gius

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Greenberger, J.S., Cagan, V.E., Peterson, J., Epperly, M.W. (2012). Radiation Protection by MnSOD-Plasmid Liposome Gene Therapy. In: Spitz, D., Dornfeld, K., Krishnan, K., Gius, D. (eds) Oxidative Stress in Cancer Biology and Therapy. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-397-4_19

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