Abstract
The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice bearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters; histologic analyses and antibody responses were only moderate and usually reversible.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Drug Synergism
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Epidermal Growth Factor / administration & dosage
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Female
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Humans
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Immunotoxins / administration & dosage
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Immunotoxins / chemistry
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Immunotoxins / pharmacology*
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Mammary Neoplasms, Experimental / drug therapy
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Mammary Neoplasms, Experimental / pathology
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Mice
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Mice, Inbred BALB C
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Ribosome Inactivating Proteins, Type 1 / administration & dosage
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Ribosome Inactivating Proteins, Type 1 / pharmacology
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Saponins / administration & dosage
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Saponins / chemistry
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Saponins / pharmacology*
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Saporins
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Treatment Outcome
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Triterpenes / administration & dosage
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Triterpenes / chemistry
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Triterpenes / pharmacology*
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Tumor Burden / drug effects
Substances
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Immunotoxins
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Ribosome Inactivating Proteins, Type 1
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Saponins
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Triterpenes
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Epidermal Growth Factor
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ErbB Receptors
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Saporins