Effect of a conjugate of daunomycin and purified polyclonal or monoclonal antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein-producing tumor cells.

Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP antibodies were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested for their antitumor activity in vitro and in vivo. They were equally cytotoxic to the rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates by either intraperitoneal or intravenous injection. Daunomycin conjugates with horse-anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than were the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal Ig. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls only slightly delayed tumor development.