Abstract
Objective To investigate the anticancer effect of the bispecific immunotoxin DTATEGF in vitro and in vivo when delivered bv convection-enhanced delivery (CED) via an osmotic minipump in a human glioblastoma brain tumor mouse xenograft model.Methods The effects of the immunotoxins were tested for their ability to inhibit the proliferation of Ln229-luc cells in vitro by methyl thiazol tetrazolium (MTT) assay.On a xenograft intracranial model,1 μg of DTATEGF or eontrol Bickel3 was delivered intracranially by CED via an osmotic minipump.The bioluminescent imaging (BLI) was performed and Kaplan-Meier survival curves were generated.The brain tumor samples were stained by hematoxylin and eosin for histopathological assessment.Results In vitro,DTATEGF could kill Ln229-luc cells and showed an 50％ inhibitory dose(IC50) less than 0.001 nmol/L.In vivo,mice with tumors were treated intracranially with drug via CED where the treatment was successful in providing a survival benefit with the median survival of mice treated with DTATEGF being significantly prolonged relative to controls (85 vs.67 days,P ＜0.01).Conclusion DTATEGF kills the Ln229-luc cell line in vitro,and when it is delivered via CED intracranially,it is highly efficacious against human glioblastoma brain tumors. Key words: Glioblastoma; Immunotherapy; Convection-enhanced delivery; Model,animal
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