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 μg or 70 μg/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 μg/mouse of free DNR showed a moderate retardation of tumor growth whereas those which received 70 μg/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.
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Abbreviations used: AFP=alpha-fetoprotein; aAFP=purified antibodies to human AFP; dex=dextran; DNR=daunorubicin; PBS=Ca2+−Mg2+-free Dulbecco's phosphate-buffered saline RV=relative tumor volume; T/C=percent ratio of RV for treated mice to RV for control
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Ohkawa, K., Hibi, N. & Tsukada, Y. Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines. Cancer Immunol Immunother 22, 81–86 (1986). https://doi.org/10.1007/BF00199119
- Tumor Growth
- Nude Mouse
- Anticancer Drug
- Tumor Cell Line