CD20 as a Target for Rheumatoid Arthritis Treatment

The FDA-approved anti-CD20 human-mouse chimeric mAb rituximab (Rituxan®) is effective against a wide variety of disorders from non-Hodgkin lymphoma (NHL) to rheumatoid arthritis. Rituximab recognizes the CD20 antigen on the surface of peripheral mature B cells and is able to induce ADCC, CDC, and apoptosis of the cells (101). Using a combination therapy approach, Daniel et al. correlated in vitro cell viability to in vivo tumor xenograft growth after treatment with rituximab with or without the Apo2 ligand/TNF-related apoptosis-inducing ligand (rhApoL/TRAIL) (102). Proapoptotic activity of rhApo2L/ TRAIL was observed for three of the seven NHL cell lines tested in vitro, and rituximab augmented rhApo2L/TRAIL-induced caspase activation in some cases (102). These results correlated well with in vivo studies, demonstrating that rhApo2L/TRAIL and rituximab cooperated to attenuate or reverse growth of tumor xenografts of the corresponding cell lines (102). In another study, Zhang et al. correlated the in vitro induction of apoptosis and caspase-3 activity caused by rituximab, and by its new hyper-cross-linked polymer formulation, to the regression of CD20+ lymphoma xenografts in vivo (103). The results confirmed that the polymer formulation of this therapeutic Ab more effectively suppressed Raji lymphoma growth in vivo relative to the native Ab in accordance with the extent of both surface CD20 clustering and caspase-3 activation, emphasizing the idea that induction of apoptosis by a hyper-cross-linked polymer can be a powerful mechanism for treating lymphomas. In support of this concept, clinical studies by Byrd et al. observed caspase-3 cleavage in

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lymphoma cells of patients treated with rituximab, suggesting the induction of apoptosis after treatment (104).

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