title: The Antitumor Effect of Single-domain Antibodies Directed Towards Membrane-associated Catalase and Superoxide Dismutase.
abstract: Neutralizing single-domain antibodies directed towards catalase or superoxide dismutase (SOD) caused efficient reactivation of intercellular reactive oxygen species/reactive nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling specifically in human tumor cells. Single-domain antibodies targeted tumor cell-specific membrane-associated SOD and catalase, but not the corresponding intracellular enzymes. They were shown to be about 200-fold more effective than corresponding classical recombinant antigen-binding fragments and more than four log steps more efficient than monoclonal antibodies. Combined addition of single-domain antibodies against catalase and SOD caused a remarkable synergistic effect. Proof-of-concept experiments in immunocompromised mice using human tumor xenografts and single-domain antibodies directed towards SOD showed an inhibition of tumor growth. Neutralizing single-domain antibodies directed to catalase and SOD also caused a very strong synergistic effect with the established chemotherapeutic agent taxol, indicating an overlap of signaling pathways. This effect might also be useful in order to avoid unwanted side-effects and to drastically lower the costs for taxol-based therapy.
authors: Institute of Virology, University Medical Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany georg.bauer@uniklinik-freiburg.de.
authors: Georg
authors: G
authors: Bauer
authors: Mikrogen-molekularbiologische Entwicklungs-GmbH, Neuried, Germany.
authors: Manfred
authors: M
authors: Motz
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D061905:Single-Domain Antibodies / Q000276:immunology*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D008565:Membrane Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D061905:Single-Domain Antibodies; D002374:Catalase; D013482:Superoxide Dismutase
keywords: RNS; ROS; SOD; Single-domain antibody; apoptosis; catalase