The effect in vivo of chemotherapeutic drug—antibody conjugates in two murine experimental tumor systems

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Abstract
Conjugates of daunomycin covalently coupled, either directly or through a dextran bridge, to antibodies reacting selectively with tumor cells, were tested for their capacity to suppress tumor development in mice. The drug—antibody conjugates, or mixtures of drug and antibody, were compared either to the free drug or to the drug coupled to normal immunoglobulin for their effect on two tumor systems. In the first case, a plasma‐cytoma (PC5), both the drug and the tumor cells were administered by the same route, namely, intraperitoneally (IP). The drug bound to antibody had no advantage over the free drug, but was better than the drug bound to normal immunoglobulin. The best results were obtained in this system when daunomycin was given in a mixture with the anti‐tumor antibody. In the second system, a lymphoma (Yac), the treatment and the tumor were administered by different routes—while the tumor was transplanted IP, the treatment was given intravenously (IV). The extent of conjugation was greatly increased in this system by introducing a dextran bridge between the drug and the antibody. In the Yac system, the anti‐tumor antibodies were purified for some of the in vivo experiments. At high doses, the daunomycin—dextran—anti‐Yac antibody conjugate was superior to the free drug but no better than daunomycin bound to dextran alone or through dextran to normal immunoglobulin. At low doses, an advantage for the binding to specific tumor antibody rather than to normal immunoglobulin was observed. On the basis of these data we believe that further improvement in the conjugation techniques, and the development of antibodies with better specificity towards the tumor cells, could lead towards successful use of antibody carriers in chemotherapy.