Targeted tumor therapy by epidermal growth factor appended toxin and purified saponin: An evaluation of toxicity and therapeutic potential in syngeneic tumor bearing mice

摘要: Targeted toxin-based therapeutics are hindered by poor intracellular uptake, limited stability and non-specific immune stimulation. To address these problems, ligand-targeted toxins in combination with low dose saponin mixtures have been adapted tested vivo the past, however, undefined raw not suitable for use clinical development. In present work we therefore used a targeted toxin (Sap3-EGF, i.e. saporin fused to epidermal growth factor) structurally defined isolated m/z 1861 (SO-1861). vitro evaluation confirmed 6900-fold enhancement cytotoxic efficacy of Sap3-EGF against TSA-EGFR target cells. The required was appreciably reduced there highly synergistic effect observed. An ex hemolysis assay showed no or very less up 10 μg/mL SO-1861. acute toxicity studies SO-1861 found be non-toxic 100 μg/treatment. enzymes aspartate aminotransferase, alanine glutamate dehydrogenase did show any statistically significant liver damage, which further histological examination. Additionally, creatinine also similar control group thus ruling out damage kidney. syngeneic BALB/c tumor model characterized EGFR overexpression were done applying 30 μg 0.1 per treatment. A more than 90% reduction (p < 0.05) average volume observed this combined therapy.