Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines

Cancer Immunol Immunother. 1986;22(2):81-6. doi: 10.1007/BF00199119.

Abstract

The anticancer drug, DNR, was conjugated to an affinity-purified horse antibody to human AFP (aAFP) via a dextran bridge. The conjugate (immunoglobulin: DNR molar ratio, 1:50) was twice as potent as free DNR in an in vitro cytotoxicity assay against an AFP-producing human yolk sac tumor. The in vivo effect of aAFP, DNR, and the conjugate was tested against the human yolk sac tumor growing in nude mice. The conjugate, at a concentration of DNR containing the equivalent amount of 20 micrograms or 70 micrograms/mouse significantly retarded tumor growth whereas free aAFP showed only a slight inhibition of tumor growth compared to the PBS-treated control. Mice which received 20 micrograms/mouse of free DNR showed a moderate retardation of tumor growth whereas those which received 70 micrograms/mouse of DNR or a mixture of DNR and aAFP showed emaciation and early death due to acute toxicity of the drug. These results suggest that the anti-body-drug conjugate accumulated preferentially on the AFP-producing tumor cells and that cytotoxicity occurred.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / therapeutic use*
  • Antibodies / toxicity
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Cell Line
  • Cytotoxicity Tests, Immunologic
  • Daunorubicin / therapeutic use*
  • Dextrans / therapeutic use*
  • Female
  • Humans
  • Mesonephroma / immunology
  • Mesonephroma / metabolism
  • Mesonephroma / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • alpha-Fetoproteins / immunology*

Substances

  • Antibodies
  • Antineoplastic Agents
  • Dextrans
  • alpha-Fetoproteins
  • Daunorubicin