THE SELECTIVE CYTOTOXICITY OF MONOCLONAL ANTIBODY CONJUGATED WITH MITOMYCIN C ON HUMAN GASTRIC CANCER CELLS

The murine monoclonal antibody (MoAb)3H11 against human gastric cancer was purified with affinity column and conjugated with Mitomycin C (MMC).The binding activity of MoAb in the conjugate retained more than 90% of the original MoAb 3H11 when the molar ratios of MMC to 3H11 was 7～8:1. The killing rate of 3H11-MMC conjugate on human gastric cancer cells BGC 823 was increased significantly than that of free MMC in vitro. The selective cytotoxicity was verified with the following results. (1) the cytotoxicity of the conjugate was much higher than that of normal mouse IgG (nMuIgG) conjugated with MMC: (2) when breast cancer cells MCF-7 was used as target cells instead of BGC 823 cells, much lower cytotoxicity of the conjugate was observed; (3) the cytotoxicity of the conjugate on BGC823 cells could be blocked when the target cells was preincubated with MoAb 3H11, but not with MoAb 3G9 which did combine with BGC823 cells at binding sites different from MoAb 3H11.Nude mice were inoculated with BGC823 cells as a model of gastric cancer and treated with conjugate 3H11-MMC, nMuIgG-MMC, MMC or PBS (ip). It was shown that thetime of tumor formation and the rate of tumor growth in 3H11-MMC conjugate treated animals were significantly different from that in control groups. The rate of inhibition of tumor weights was 60.4% for the conjugate 3H11-MMC treated group which was significantly higher than for other groups.