Re-Evaluation of CD37 As Target for Radioimmunotherapy of Non-Hodgkin Lymphoma,

Abstract 3732

The monoclonal anti-CD20 antibody rituximab alone or as part of combination therapy, is considered standard therapy for non-Hodgkin's B-cell lymphomas. However, significantly better clinical results have been obtained for beta-emitting anti –CD20 radioimmunoconjugates (RICs) than for rituximab. RICs targeting CD20 may be problematic because of antigenic drift and antigen blocking caused by previous treatments with rituximab. Therefore, novel therapeutic approaches targeting other B cell antigens might be more effective after rituximab treatment failure than a new anti-CD20 treatment. In the present study, we have compared the therapeutic effect of the novel anti-CD37 RIC ¹⁷⁷Lu-DOTA-HH1 with the anti-CD20 RIC ¹⁷⁷Lu-DOTA-rituximab against Daudi human lymphoma cells in vitro and in vivo. At the same antibody concentration ¹⁷⁷Lu-DOTA-HH1 was significantly more effective in inhibiting cell growth in vitro than ¹⁷⁷Lu-DOTA-rituximab. SCID mice were intravenously injected with 10 million Daudi cells one week before RIC treatment. A significantly increased survival of mice treated with ¹⁷⁷Lu-DOTA-HH1 as compared with ¹⁷⁷Lu-DOTA-rituximab treatment was observed. Furthermore, the toxicity of the ¹⁷⁷Lu-DOTA-HH1 treatment was significantly lower than for ¹⁷⁷Lu-DOTA-rituximab. In addition, we have compared binding properties and biodistribution of HH1 with rituximab. The affinity of HH1 to CD37 was similar to the affinity of rituximab to CD20. The CD37-HH1 complex was internalized 10 times faster than CD20-rituximab. Both antibodies had a relevant biodistribution and low uptake in bone. This work warrants further preclinical and clinical studies with ¹⁷⁷Lu-HH1.