CHIMERIC ANTI-CD20 (IDEC-C2B8) MONOCLONAL-ANTIBODY SENSITIZES A B-CELL LYMPHOMA CELL-LINE TO CELL-KILLING BY CYTOTOXIC DRUGS

More than 50% of patients with aggressive B lymphomas and the majority of patients with low grade lymphomas are not cured by current therape utic strategies. The lymphomas express the B cell antigen CD20 on the cell surface and this antigen serves as target for antibody-directed t herapies. Clinical studies with encouraging results have been underway with tile use of a chimeric anti-CD20 antibody (IDEC-C2B8), consistin g of human IgG1-6 constant regions and variable regions from the murin e monoclonal anti-CD20 antibody IDEC-2B8. this study investigated the potential anti-tumor therapeutic value of combination treatment with a nti-C2B8 and cytotoxic drugs. The in vitro study examined the sensitiz ing effect of C2B8 antibody on the DHL-4 B lymphoma line to various cy totoxic agents. Cytotoxicity was determined by, the MTT assay. Surface and cytoplasmic proteins were determined by flow cytometry. Pretreatm ent of DHL-4 with C2B8 resulted in inhibition of cell proliferation an d cell death and a fraction of the cells underwent apoptosis. While th e DHL-4 tumor cells were relatively resistant to several cytotoxic dru gs, pretreatment with C2B8 rendered the cells sensitive to TNF-alpha r icin, diphtheria toxin (DTX), adriamycin and cisplatin but not to VP-1 6. Chemosensitization of DHL-4 tumor cells was not due to downmodulati on of either the MDR-1 or bcl-2 gene products. However, treatment of D HL-4 with C2B8 inhibited TNF-alpha secretion. These findings demonstra te that C2B8 antibody, potentiates the sensitivity of DHL-4 tumor cell s to several cytotoxic agents. Further, the findings suggest that comb ination treatments with C2B8 antibody and drugs may be of clinical ben efit in the treatment of patients with resistant aggressive B lymphoma s.