Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines.
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.
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003630:Daunorubicin / Q000627:therapeutic use*; D003911:Dextrans / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008649:Mesonephroma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000509:alpha-Fetoproteins / Q000276:immunology*
D000906:Antibodies; D000970:Antineoplastic Agents; D003911:Dextrans; D000509:alpha-Fetoproteins; D003630:Daunorubicin