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>Development of an Immunoassay for BMS-191352, A Single-Chain Immunotoxin, and Its Application to Toxicokinetic Studies
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Development of an Immunoassay for BMS-191352, A Single-Chain Immunotoxin, and Its Application to Toxicokinetic Studies
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机译：Development of an Immunoassay for BMS-191352, A Single-Chain Immunotoxin, and Its Application to Toxicokinetic Studies
BMS-191352 is a single-chain fusion protein composed of the variable regions of chimeric BR96 monoclonal antibody and the binding defective form ofPseudomonasExotoxin A (PE40). The immunotoxin exhibits potent cytotoxicity against tumor cells expressing the LewisYantigen. A sensitive and specific double antibody sandwich ELISA has been developed and validated for the determination of BMS-191352 in rat and dog EDTA plasma. A monoclonal anti-PE40 antibody (EXA2-1H8) was used to capture BMS-191352 in plasma samples. The captured BMS-191352 was then detected using a biotinylated monoclonal BR96 anti-idiotypic antibody (757-4-1) followed by the addition of streptavidin-horseradish peroxidase conjugate and chromogen 3, 3#x2032;, 5, 5#x2032;-tetramethylbenzidine. The optical density was measured at 450 nm. The standard curve range in rat and dog plasma was 2#x2013;32 ng/mL. The RSD for the inter- and intra-assay precision was within 9.2 and the accuracy was greater than 89.0. The ELISA method was applied to the analysis of BMS-191352 in plasma samples from toxicokinetic studies conducted in rats and dogs. These studies revealed that the systemic exposure of BMS-191352 was dose proportional and the kinetics of BMS-191352 were linear between the dose range of 1.8#x2013;7.2 mg/m2in the rat and 2.5#x2013;15 mg/m2in the dog.
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