GROWTH-INHIBITION OF CD20-POSITIVE B-LYMPHOMA CELL-LINES BY IDEC-C2B8ANTI-CD20 MONOCLONAL-ANTIBODY

Treatment with IDEC-C2B8 (C2B8), the chimeric anti-CD20 antibody, was shown in a phase B-LI study to be very effective for the treatment of low-grade B-cell lymphoma, in contrast to the results of most previous immunotherapies with monoclonal antibodies. In a study designed to el ucidate the reason for this efficacy, two cell lines derived from lymp homas with BCL2 gene rearrangement (SU-DHL-4 and SU-DHL-6) showed rema rkable growth inhibition and cell-death, and two other cell lines deri ved from a diffuse lymphoma (RC-K8) and a mantle cell lymphoma (SP-49) showed moderate growth inhibition, but neither a CD20 weakly positive cell line (NALL-1) nor a negative cell line (MOLT-4) showed any growt h inhibition. An examination of the intensity of cull-surface CD20 exp ression showed no correlation between intensity and degree of growth i nhibition among the four cell lines showing growth inhibition, Morphol ogical examination revealed condensed and fragmented nuclei and buddin g of the plasma membrane, both characteristic of apoptosis, with some cells in these cell lines showing growth inhibition by C2B8. Such apop tosis was also confirmed by flow cytometric analysis, suggesting that, at least in part, apoptosis plays a role in this growth inhibition. T his growth-inhibitory mechanism mag thus account for the effectiveness of C2B8 antibody therapy.