New Application of Human Tumor Clonogenic Assay to in Vitro Evaluation of Tumor-Targeting Efficiency of Immunoconjugates

概要

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This report proposes an efficient in vitro method for the evaluation of drug targeting with monoclonal antibody as a carrier to tumor cells. Monoclonal antibody (35G; IgG_<2a>) selectively binding to α-fetoprotein (AFP) from human hepatoma cells (HuH-7) was conjugated with an anticancer drug, vindesine (VDS). Human tumor clonogenic assay (HTCA) with some modifications was applied to estimate the targeting efficiency of a conjugate (VDS-35G) for the first time. In this assay, VDS-35G was cytotoxically active against HuH-7 cells at a lower concentration (0.5 ng/ml) and for a shorter contact time than VDS (50 ng/ml), while 35G and VDS-normal mouse immunogloblin conjugate (VDS-n-IgG) were not active against the cells. Both VDS-35G and VDS-n-IgG were inactive against HuH-13 cells established from a human hepatocellular carcinoma producing no AFP. In the conventional monolayer culture assay (MCA), VDS-35G showed little effect on HuH-7 cells at the concentration effective in HTCA. The cytotoxic activity of VDS in MCA was similar to that in HTCA but the cytotoxic activity of VDS-35G in MCA was considerably different from that in HTCA. This discrepancy could be explained by the hypothesis that VDS-35G was directed at stem cells of the HuH-7 cell population sensitively and selectively. HTCA was shown to be a useful in vitro evaluation method for drug targeting.
公益社団法人日本薬学会の論文
1992-08-25