Therapy of disseminated B-cell lymphoma xenografts in severe combined immunodeficient mice with an anti-CD74 antibody conjugated with (111)indium, (67)gallium, or (90)yttrium

A radiolabeled antibody (Ab) to CD74 (the MHC class II invariant chain, Ii) was shown previously to effectively kill human B-lymphoma cells in vitro. Conjugates with both Auger electron and P-particle emitters were able to ki ll cells, but the former displayed less nonspecific toxicity in the kt vitr o assay used. In this report, we have extended the studies to an in vivo mo del of tumor growth. The human B-cell lymphoma Raji was injected i,v, into severe combined immunodeficient mice, and radiolabeled Abs were injected at various times after tumor inoculation. The maximum tolerated dose (MTD), a s well as lower doses, was tested, Tumor growth was monitored by hind-leg p aralysis. With a 3-5-day interval before Ab injection, anti-CD74 conjugated to either In-111 or Ga-67, at a dose of 240-350 mu Ci/mouse, produced a st rong therapeutic effect, with greatly delayed tumor growth, and many of the treated mice were tumor free for >6 months. Control mice became paralyzed in 16-24 days, uniformly, Treatment at later time points (9-day interval) h ad little therapeutic effect. The MTD was required for optimal therapy. Wit h the P-particle emitter Y-90, the MTD was much less, 25 mu Ci/mouse, and a t this dose there was only a weak therapeutic effect. In conclusion, the da ta suggest that low-energy electrons are more effective than P-particles in this model system. These results may be applicable to humans, particularly in the case of micrometastatic disease. This approach may also be effectiv e with other Abs that accrete in large amounts,