Biodistribution of HuCC49DeltaCH2-beta-galactosidase in colorectal cancer xenograft model.

International Journal of Pharmaceutics
Yanke YuDuxin Sun

Abstract

Antibody-enzyme conjugate (AbE) has been widely studied for site-specific prodrug activation in tumors. The purpose of this study is to characterize the pharmacokinetics and tissue distribution of HuCC49DeltaCH2-beta-galactosidase conjugate. HuCC49DeltaCH2 and beta-galactosidase were chemically conjugated and injected into a LS 174T colon cancer xenograft model. A colorimetric assay was developed to quantify the HuCC49DeltaCH2-beta-galactosidase levels in plasma and tissues. The HuCC49DeltaCH2-beta-galactosidase conjugate distributed into tumor tissue as early as 6h with the tumor/blood ratio of 5. This favored distribution of conjugate activity in the tumor tissue which was maintained up to 4 days post conjugate injection, while the conjugate was cleared rapidly from blood and other normal tissues (heart, spleen, lung, liver, kidney and stomach). At a high dose of 3000 U/kg, HuCC49DeltaCH2-beta-galactosidase conjugate saturated the antigen binding sites and yielded decreased tumor/normal tissue ratios compared to 1500 U/kg. These data suggest that HuCC49DeltaCH2-beta-galactosidase specifically target to the tumors to increase tumor selectivity.

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