Antibody-CD20-interferon-alpha fusion protein has superior in vivo activity against human B cell lymphomas compared to Rituximab, and enhanced complement-dependent cytotoxicity in vitro

Results Anti-CD20-hIFNa induced stronger growth inhibition than rituximab, particularly against Burkitt and germinal center-type DLBCL NHLs. Tumor growth inhibition by anti-CD20-hIFNa was associated with substantial apoptosis in some cell lines. Anti-CD20-hIFNa exhibited potent ADCC activity against Daudi, Ramos, and Raji cells, identical to rituximab. Surprisingly, anti-CD20-hIFNa exhibited superior CDC compared to rituximab against Daudi, Ramos, and Raji cells that was dependent upon linkage of IFNa to the anti-CD20 antibody, and correlated with improved complement fixation. Importantly, against Raji NHL xenograft tumors in SCID mice, anti-CD20-hIFNa achieved superior efficacy compared to rituximab (p=0.0015) and control fusion protein (p<0.0001). At antibody doses at which Raji xenograft tumors progressed through rituximab, anti-CD20-hIFNa eradicated 50-88% of established tumors. Non-targeted control fusion protein had only minor effects on tumor growth.