Rituximab

Rituximab is a chimeric anti-CD20 monoclonal antibody. CD20 is a cell-surface protein that occurs almost exclusively on mature B-cells. The main mechanisms of its actions are complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and induction of apoptosis. It is highly effective in the treatment of CD20-positive B-cell lymphoma such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Rituximab can be easily combined with conventional combination chemotherapies such as cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). Rituximab with CHOP (R-CHOP) could improve the survival of DLBCL, and R-CHOP was established as a standard treatment for DLBCL As for FL, the use of combining rituximab with chemotherapy was superior to chemotherapy alone, and is considered standard treatment. Also rituximab maintenance therapy could improve the treatment results of patients with FL who were treated with rituximab monotherapy, combination chemotherapies and rituximab-containing chemotherapies. Some patients with B-cell lymphoma are resistant to rituximab, and the mechanisms remain to be elucidated. We found that some B-cell lymphoma cells lost their CD20 expression at relapse or progression after rituximab treatment. We have successfully established a B-cell line from a patient with B-cell lymphoma who showed CD20-negative relapse after rituximab treatment. The expressions of CD20 mRNA and protein in this cell line were stimulated when the cells were treated with 5-aza-2′-deoxycytidine (decitabine). These findings suggest that some epigenetic mechanisms may be partly related to the down regulation of CD20 expression after rituximab treatment. Further studies on the mechanisms of CD20-negative relapse will overcome the rituximab-resistance in some B-cell lymphoma patients.