[Studies of two conjugates of monoclonal antibody (HIM6) and cytosine arabinoside]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1993 Aug;15(4):286-90.
[Article in Chinese]

Abstract

Two conjugates (HIM6-PAD-ara C and HIM6-PLGA-ara C) of the anticancer agent cytosine arabinoside (ara C) and monoclonal antibody (HIM6) against human leukocytes were prepared with dextran T-40 and poly-L-glutamic acid as intermediate carriers, respectively. The drug-antibody conjugates maintained most of the original antigen-binding activity of the free antibody. The ratio of positive bound cells was found to be > 90% by an indirect immunofluorescence assay. The cytotoxicities of HIM6-PAD-ara C and HIM6-PLGA-ara C against antibody-reactive human leukemia HL60 cells were lower than those of free ara C and a mixture of ara C and HIM6 (IC50s of HIM6-PAD-ara C, HIM6-PLGA-ara C, ara C and the mixture of ara C and HIM6 were 0.212, 0.102, 0.028 and 0.024 microgram/ml, respectively), but were similar to those of the intermediates PAD-ara C and PLGA-ara C. On the other hand, these two conjugates showed no cytotoxic its against non-target hepatoma cells. These results indicate that the specific cytotoxicity of the conjugate depends on specific binding to the target surface antigen by the monoclonal antibody in the conjugate molecule.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Carcinoma, Hepatocellular / pathology
  • Cytarabine / pharmacology*
  • Dextrans
  • Drug Carriers
  • Humans
  • Immunotoxins / pharmacology*
  • Leukemia, Promyelocytic, Acute / pathology*
  • Liver Neoplasms / pathology
  • Polyglutamic Acid
  • Tumor Cells, Cultured / drug effects

Substances

  • Antibodies, Monoclonal
  • Dextrans
  • Drug Carriers
  • Immunotoxins
  • Cytarabine
  • Polyglutamic Acid