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- W4241275737 abstract "We examined the in vivo efficacy of targeting β-glucuronidase (βG) to activate a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at hepatoma ascites in Sprague-Dawley rats. Injection i.p. of 500 μg RH1-βG, a conjugate formed between recombinant βG and monoclonal antibody RH1 with specificity for an antigen expressed on AS-30D rat hepatoma cells, into rats bearing AS-30D ascites resulted in the accumulation of 54 μg conjugate per 109 tumor cells after 2 hr. Ascites fluid and serum contained 0.53 and 0 μg/ml, respectively, RH1-βG 2 hr after injection of the conjugate. Conjugate binding to AS-30D cells was heterogeneous and non-saturated, as determined by flow cytometry. BHAMG was less toxic than pHAM to SD rats based on measures of animal mortality, weight loss and hematological toxicity. Treatment of rats bearing established hepatoma ascites with 500 μg RH1-βG followed 2 hr later with a single i.p. injection of 30 mg/kg BHAMG or 3 i.p. injections of 10 mg/kg BHAMG 2, 3 and 4 hr later resulted in the cure of 6/8 and 8/8 animals, respectively. Treatment with BHAMG or pHAM alone did not produce cures, whereas treatment with a control antibody–βG conjugate and BHAMG produced significantly greater hematological toxicity compared to treatment with RH1-βG and BHAMG. All cured rats were completely protected from rechallenge with 2 × 107 AS-30D cells, indicating that successful treatment of animals induced protective immunity. Int. J. Cancer 73:392–402, 1997. © 1997 Wiley-Liss, Inc." @default.
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- W4241275737 date "1997-11-04" @default.
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- W4241275737 title "Cure of malignant ascites and generation of protective immunity by monoclonal antibody–targeted activation of a glucuronide prodrug in rats" @default.
- W4241275737 doi "https://doi.org/10.1002/(sici)1097-0215(19971104)73:3<392::aid-ijc14>3.3.co;2-6" @default.
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