The anti-CD20 monoclonal antibody, rituximab, provides a significant therapeutic benefit for patients with B-cell disorders. However, response to therapy varies and relapses are common, so an understanding of both inherited and acquired rituximab resistance is needed. In order to identify mechanisms of inherited resistance, sensitive versus resistant individuals were selected from a survey of 9...

Current therapies for non-Hodgkin lymphoma commonly include CD20 mAb to deplete tumor cells. However, the response is not durable in a substantial proportion of patients. Herein, we report our studies in mice testing the hypothesis that heterogeneity in endogenous tissue CD20+ B cell depletion influences in vivo lymphoma therapy. Using highly effective CD20 mAbs that efficiently deplete endogen...

Incubation of Burkitt lymphoma-derived Raji cells at physiological temperature with submicromolar concentrations of humanized anti-CD20 antibody rituximab (RTX) redistributes CD20 to liquid-ordered, plasma membrane rafts. This accumulation of the CD20 tetraspan protein in rafts does not change the existing lipid and phosphoprotein composition but makes sphingolipids and the Src regulator Cbp/PA...

Rituximab is the first anti-cancer antibody approved by the FDA for the treatment of B-cell non-Hodgkin lymphoma (B-NHL), alone or in combination with chemotherapeutic drugs. Further, rituximab is now being examined in a variety of CD20+ neoplastic diseases as well as B-cell-induced autoimmune diseases. The clinical response to rituximab is significant, resulting not only in tumor regression bu...

Rituximab (chimeric anti-CD20 monoclonal antibody) is widely employed in the treatment of patients with B cell non-Hodgkin lymphoma (NHL). This agent has activity in both indolent and aggressive disease, alone and in combination with chemotherapy. Unfortunately, however, many patients develop resistant disease. Ongoing efforts to improve outcomes include changes in dose and schedule, as well as...

Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of different haematological cancers with a wide range of aggressiveness. NHLs represent >80% of lymphomas and the majority of NHLs involve B cells. CD20 represents a good target for NHL immunotherapy because it is largely expressed on B cell NHL and not on B cell precursors and plasma cells. The anti-CD20 monoclonal antibody (mAb) rituxim...

Autoimmune diabetes is believed to be mediated primarily by T cells. However, B cells have been implicated in the pathogenesis of the disease in NOD mice. Although preclinical studies have been limited by the absence of anti-CD20 reagents that can induce B cell depletion in mice, a clinical trial using the B cell-depleting anti-CD20 monoclonal antibody rituximab (Rituxan) is underway in type 1 ...

BACKGROUND The loss of CD20 protein expression after a rituximab-containing regimen is one of the resistance mechanisms in non-Hodgkin's lymphoma. Recently, it was reported that 5-azacitidine administration upregulates the expression of CD20 in CD20-negative B-cell acute lymphoblastic leukemia. Here we report a similar upregulation in a patient with follicular lymphoma who was treated with 5-az...

Acquirement of resistance to rituximab has been observed in lymphoma patients. To define mechanisms associated with rituximab resistance, we developed various rituximab-resistant cell lines (RRCL) and studied changes in CD20 expression/structure, lipid raft domain (LRD) reorganization, calcium mobilization, antibody-dependent cellular cytotoxicity, and complement-mediated cytotoxicity (CMC) bet...

The anti-CD20 monoclonal antibody (mAb) rituximab has been used successfully for lymphoma therapy for more than 10 years. Although several direct mechanisms by which anti-CD20 mAbs act have been characterized in vitro, their specific role in clinical efficacy is still debated. Little is known about the possible antitumor immune response that they may induce in patients, despite clinical data su...