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|Title:||Preparation and in vitro cytotoxic evaluation of taxol immunoconjugates|
Rao, Y Madhusudan
|Series/Report no.:||Int. Cl.⁸ A01N63/00; C12N15/00|
|Abstract:||The taxol (paclitaxel) immunoconjugates prepared by derivatizing the taxol at two positions and linking the Mab CIBCNSH3 against EGF receptors were tested for in vitro cytotoxicity. Succinyl derivatives of taxol at 2'-OH and 7-OH groups were prepared as per the published procedures. Both the products were purified by column chromatography. The 7-succinyl taxol and 2'-succinyl taxol immunoconjugates were prepared with CIBCNSH3, Mab against EGF receptor using a published procedure involving water soluble EDC. The unbound taxol derivatives were separated either by dialysis or centricon separators. The drug to antibody ratio was estimated by either extracting the linked drug after hydrolysis of a conjugate or simultaneous Beer’s law. The Drug-immunoconjugates were tested for their in vitro cytotoxic effect on EGF receptor expressing cells either A-549 or MCF-7 and HBL-100 by using MTT protocol and the IC₅₀ values were calculated. The drug to antibody ratio was 0.45:1 for 7-succinyl taxol, and 0.38:1 for 2'-succinyl taxol. The IC₅₀ value was 78 nM on A-549 cells for 7-succinyl taxol conjugate, while for 2'-succinyl taxol conjugate the IC₅₀ values were 114.8 nM and 120.3 nM on MCF-7 and HBL-100 cells respectively. Overall, as compared to the pure antibody both taxol immunoconjugates showed more cytotoxic activity.|
|Appears in Collections:||IJBT Vol.06(4) [October 2007]|
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