![]() This review focuses on the current understanding of the mechanism of action of rituximab and suggests ways to improve its clinical efficacy. A better understanding of rituximab-induced cell killing will allow the development of new, more effective antibodies derived from rituximab as well as innovative treatment modalities designed to optimize its mechanisms of action through selection of the most sensitive tumors, potentiation of cytotoxicity mechanisms or neutralization of resistance, design of optimal dosing schedules, and finding the best synergies. ![]() Several recent studies on CD20 structure and downstream signaling pathways have put forward key arguments that have helped to elucidate the in vivo mechanisms of action of rituximab. It is therefore difficult to evaluate the respective contribution of each of these effects that, moreover, could have different contributions according to lymphoma subtype. Most of these studies were performed with CD20 + cell lines in vitro and in murine models and in some cases with fresh neoplastic B cells in vitro. Other studies have suggested that rituximab may have a “vaccinal” effect. In vitro data suggest that it induces apoptosis, complement-mediated lysis (complement-dependent cytotoxicity ), and antibody-dependent cellular cytotoxicity (ADCC) and some studies seem to confirm the involvement of these mechanisms in vivo. Rituximab has become the hallmark of anticancer mAbs, which offer a new approach to the treatment of B-cell lymphoproliferative disorders.Īlthough the clinical effectiveness of rituximab is no longer in question, its in vivo mechanisms of action have yet to be elucidated. Rituximab has some therapeutic activity in antibody-based autoimmune diseases, 2 and its indications are likely to be extended in the next few years. It is the first approved targeted treatment in the field of oncology and its impact on the treatment of NHL is evidenced by the short interval between its initial description 1 and its approval by both American and European authorities (19, respectively). 1 Rituximab is currently indicated in both follicular and aggressive B-cell non-Hodgkin lymphomas (NHL). ![]() Rituximab was created by fusing the light- and heavy-chain variable domains of 2B8, a murine monoclonal anti-CD20 antibody and human κ light-chain and γ1 heavy-chain constant regions. It binds specifically to CD20, an antigen expressed by most human B lymphocytes. Rituximab is a chimeric monoclonal antibody (mAb) produced by recombinant technology. A better understanding of how rituximab acts in vivo should make it possible to develop new and more effective therapeutic strategies. Here, we review the current understanding of the mechanism of action of rituximab and discuss approaches that could increase its clinical activity. Rituximab also has a delayed therapeutic effect as well as a potential “vaccinal” effect. Rituximab has been shown to induce apoptosis, complement-mediated lysis, and antibody-dependent cellular cytotoxicity in vitro, and some evidence points toward an involvement of these mechanisms in vivo. Despite its demonstrated clinical effectiveness, its in vivo mechanisms of action remain unknown and could differ by subtype of lymphoma. Rituximab is currently used in the treatment of both follicular and aggressive B-cell non-Hodgkin lymphomas. Rituximab (MabThera, Rituxan) is a chimeric IgG1 monoclonal antibody that specifically targets the CD20 surface antigen expressed on normal and neoplastic B-lymphoid cells.
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