Understanding rituximab function and resistance: implications for tailored therapy.
نویسندگان
چکیده
The addition of anti-CD20 monoclonal antibody (rituximab) to chemotherapy has significantly improved survival in B-cell lymphoma. However, a substantial number of patients relapse after treatment with rituximab. Understanding of anti-CD20 antibody molecular function may facilitate the development of pharmacologic strategies to overcome resistance. Cell death have been demonstrated to be caused by rituximab binding to CD20 throughout direct and indirect mechanisms. The direct mechanism comprises growth inhibition, induction of apoptosis and sensitization of cells to chemotherapy. While, the indirect mechanisms to Rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). However, these mechanisms are still poorly understood. To shed light on this issue, we have analyzed the most significant results showing the role of Rituximab as a signal-inducing antibody and as a chemosensitizing agent through negative regulation of major survival pathways. Mechanisms of resistance to Rituximab are also discussed. Additionally, studies here reported show that, cellular targets are modified after treatment with Rituximab and may become useful for novel therapeutic strategies in the treatment of patients resistant to standard therapy.
منابع مشابه
Physicochemical evaluation of lyophilized formulation of p-SCN-Bn-DOTA-and p-SCN-Bn-DTPA-rituximab for NHL radioimmunotherapy
Radioimmunotherapy (RIT) of Non-Hodgkin’s lymphoma (NHL) is said to be more advantageous compared to unlabelled therapeutic antibodies. To this date, radiolabelled murine anti-CD20 mAbs, Zevalin® and Bexxar® have been approved for imaging and therapy. A preparation containing rituximab, chimeric mAb radioimmunoconjugate suitable for Lu-177 labeling, could provide better imaging and therapeutic ...
متن کاملRituximab Is Indispensable for Pediatric Heart Transplant Recipients Developing Post transplant Lymphoproliferative Disorders
Abstract Rituximab, an anti-CD20 agent, has been suggested as an effective strategy to deal with post transplant lymphoproliferative disorders (PTLD). In the current study, we aim to evaluate the efficacy of rituximab therapy in heart transplant population developing PTLD. A comprehensive search of the literature was performed to gather the available data on lymphoproliferative disorders oc...
متن کاملThe role of complement in the mechanism of action of rituximab for B-cell lymphoma: implications for therapy.
Rituximab, a genetically engineered chimeric monoclonal antibody specifically binding to CD20, was the first antibody approved by the U.S. Food and Drug Administration for the treatment of cancer. Rituximab significantly improves treatment outcome in relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). However, there are also some challenges for us to overcome: w...
متن کاملEvaluation of the efficacy and safety of rituximab in patients with refractory pemphigus vulgaris
Background: Recently, rituximab has been successfully used for the treatment of pemphigus family, the main subtype of which is pemphigus vulgaris (PV). The aim of this study was to determine the efficacy and safety of rituximab in refractory PV. Methods: In an observational study extending from November 2014 to February 2016, 30 patients with refractory PV were treated with rituximab. Response ...
متن کاملCombined Therapy for Anti-N-methyl D-aspartate Receptor Encephalitis
Background Anti-N-methyl- d-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune neurological disorder that usually occurs as a paraneoplastic syndrome and is particularly associated with ovarian teratoma. Standard therapy for severe cases is not established and the prognosis in patients who do not respond to first-line treatment is poor. Case Report An 11-year-old boy complained ps...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Frontiers in bioscience
دوره 16 شماره
صفحات -
تاریخ انتشار 2011