A study was undertaken to investigate the efficacy of a high affinity, rapidly internalizing anti-CD22
monoclonal antibody for selectively delivering high-energy (90)Y radioactivity to B
lymphoma cells in vivo. The antibody, RFB4, was readily labeled with (90)Y using the highly stable chelate, 1B4M-diethylenetriaminepentaacetic
acid. Labeled RFB4 selectively bound to the CD22(+)
Burkitt's lymphoma cell line Daudi, but not to CD22(-) control cells in vitro as compared with a control antibody, and was more significantly bound (P = 0.03) to Daudi solid
tumors growing in athymic nude mice. Biodistribution data correlated well with the antitumor effect. The
therapeutic effect of (90)Y-labeled anti-CD22 (Y22) was dose-dependent, irreversible, and the best results were achieved in mice receiving a single i.p. dose of 196 microCi. These mice displayed a significantly better (P < 0.01) antitumor response than control mice and survived >200 days with no evidence of
tumor. Histology studies showed no significant injury to kidney, liver, or small intestine. Importantly,
tumor-bearing mice treated with Y22 had no radiologic bone marrow damage compared with
tumor-bearing mice treated with the control-labeled antibody arguing that the presence of CD22(+)
tumor protected mice from bone marrow damage. When anti-CD22
radioimmunotherapy was compared to
radioimmunotherapy with anti-CD19 and anti-CD45
antibodies, all three
antibodies distributed significantly high levels of
radioisotope to flank
tumors in vivo compared with controls (P < 0.05), induced complete remission, and produced long-term,
tumor-free survivors. These findings indicate that anti-CD22
radioimmunotherapy with Y22 is highly effective in vivo against CD22-expressing
malignancies and may be a useful
therapy for
drug-refractory
B cell leukemia patients.