ERADICATION OF LARGE HUMAN B-CELL TUMORS IN NUDE-MICE WITH UNCONJUGATED CD20 MONOCLONAL-ANTIBODIES AND INTERLEUKIN-2

Since antibody-dependent cellular cytotoxicity is considered an import ant mechanism by which mAbs may exert their antitumor effects, it seem s likely that these antitumor effects can be enhanced by the activatio n of the appropriate effector cell populations. We have used nude mice xenografted with human Daudi tumor cells as a model to compare the an tilymphoma effects of unconjugated CD19 (CLB-CD19) and CD20 (BCA-B20) mAbs (IgG2a subclass) alone or in combination with recombinant human i nterleukin 2 (rhIL-2) or recombinant mouse granulocyte-macrophage-colo ny-stimulating factor (rmGM-CSF). Treatment of established tumors with BCA-B20 or rhIL-2 or rmGM-CSF as a single agent, all resulted in high ly significant decreases of tumor growth rates, but did not increase t he number of complete regressions. The combination of CLB-CD19 or BCA- B20 mAbs with rhIL-2 or rmGM-CSF resulted in larger decreases of growt h rates than either of the agents alone. Complete eradication of large Daudi tumors could be achieved when treatment with BCA-B20 mAbs was c ombined with rhIL-2 but not with the combination of CLB-CD19 mAbs and rhIL-2 nor with the combination of BCA-B20 mAbs and rmGM-CSF. Cured an imals kept for 2-3 months after complete regression of the tumors were still tumor free. Regression of tumors was correlated with the infilt ration of lymphocytes as well as macrophages into the tumor. This is t he first report to show that unconjugated CD20 mAbs are to be preferre d over unconjugated CD19 mAbs, and interleukin 2 over GM-CSF in the co mbinational treatment of large B cell tumors.