Mechanism of Action of Rituximab
Rituximab causes B-cell lysis by binding to the CD20 antigen on the surface of B cells, resulting in their destruction through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). 1
Primary Mechanism of Action
- Rituximab is a chimeric monoclonal antibody that specifically targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes 1, 2
- Upon binding to CD20, rituximab mediates B-cell lysis through multiple mechanisms 1:
Effects on B Cells
- CD20 is expressed on >90% of B-cell non-Hodgkin's lymphomas and to a lesser degree on B-cell chronic lymphocytic leukemia cells 5
- Rituximab causes rapid and sustained depletion of circulating and tissue-based B cells that is maintained for at least 6-12 months 2, 1
- B-cell recovery typically begins at approximately 6 months with median B-cell levels returning to normal by 12 months following completion of treatment 1
Clinical Applications
- Rituximab has become a dominant component of treatment regimens for various B-cell malignancies 2
- It is used in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and other B-cell malignancies 1, 5
- The National Comprehensive Cancer Network recommends an initial dosing of 375 mg/m² administered intravenously once weekly for 4 weeks for patients with non-Hodgkin's lymphoma 6
- Rituximab is also used in autoimmune disorders due to its ability to deplete B cells that contribute to autoimmune pathology 7
Molecular Effects
- Rituximab binding to CD20 leads to lipid raft modifications in the cell membrane 4
- It activates various kinases and caspases involved in cell death pathways 4
- The drug affects transcription factors and modifies the balance between apoptotic and anti-apoptotic molecules 4
- Rituximab can sensitize cancer cells to chemotherapy, enhancing the effectiveness of combination treatments 3, 8
Important Clinical Considerations
- Response to rituximab varies among patients, with some developing resistance 3, 4
- Potential resistance mechanisms include expression of complement inhibitors CD55 and CD59 on tumor cells 3
- Infusion-related reactions are common but usually mild to moderate; approximately 10% of patients may develop severe reactions 5
- Monitoring for viral reactivation, particularly hepatitis B virus, is recommended during treatment 6
In summary, rituximab works by targeting CD20-positive B cells and facilitating their destruction through multiple immune-mediated and direct cellular mechanisms, making it an effective treatment for various B-cell malignancies and certain autoimmune conditions.