From the Guidelines
Rituximab is a chimeric monoclonal antibody that targets the CD20 antigen found on the surface of B lymphocytes, leading to B cell depletion through complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and direct induction of apoptosis. The mechanism of action of rituximab involves binding to CD20 on B cells, which results in the destruction of these cells through several pathways, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and direct induction of apoptosis (programmed cell death) in some B cell populations 1. Rituximab specifically targets CD20-positive B cells, which include pre-B cells and mature B cells, but spares stem cells, pro-B cells, and plasma cells since they don't express CD20, allowing for eventual B cell recovery from stem cells while maintaining some antibody production from plasma cells during treatment 1. The depletion of B cells reduces the production of autoantibodies, cytokines, and other inflammatory mediators, making rituximab effective for treating B cell malignancies like non-Hodgkin lymphoma and chronic lymphocytic leukemia, as well as autoimmune disorders such as rheumatoid arthritis, granulomatosis with polyangiitis, and pemphigus vulgaris 1. Key points about rituximab's mechanism of action include:
- Binding to CD20 antigen on B cells
- Induction of B cell depletion through CDC, ADCC, and apoptosis
- Selective targeting of CD20-positive B cells, sparing stem cells, pro-B cells, and plasma cells
- Eventual B cell recovery from stem cells during treatment
- Reduction in autoantibody, cytokine, and inflammatory mediator production
- Efficacy in treating B cell malignancies and autoimmune disorders 1.
From the FDA Drug Label
Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC)
The mechanism of action of Rituximab is through binding to the CD20 antigen on pre-B and mature B-lymphocytes, leading to B-cell lysis. The possible mechanisms of cell lysis include:
- Complement dependent cytotoxicity (CDC)
- Antibody dependent cell mediated cytotoxicity (ADCC) 2
From the Research
Mechanism of Action of Rituximab
The mechanism of action of rituximab involves several key processes:
- Complement-dependent cytotoxicity (CDC): Rituximab binds to the CD20 antigen on B cells, activating the complement system and leading to cell lysis 3, 4, 5.
- Antibody-dependent cellular cytotoxicity (ADCC): Rituximab also induces ADCC, where immune cells such as natural killer cells and macrophages recognize and destroy B cells coated with rituximab 4, 6.
- Apoptosis: Rituximab can induce apoptosis, or programmed cell death, in B cells 3, 4, 5.
- Direct growth arrest: Rituximab may also directly inhibit the growth of B cells 5.
Key Findings
- Studies have shown that CDC is a major mechanism of action of rituximab, with ADCC and apoptosis playing secondary roles 3, 4.
- The effectiveness of rituximab can be enhanced by combining it with other therapies, such as chemotherapy or neutralization of complement regulatory proteins 4, 5.
- Resistance to rituximab therapy can occur, and strategies to overcome this resistance are being developed, including the use of neutralizing antibodies to CD55 and CD59 4, 5.
Clinical Implications
- Rituximab has been shown to be effective in the treatment of B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma 4, 6, 7.
- Rituximab has also been used to treat other conditions, including rheumatoid arthritis, autoimmune hemolytic anemia, and nephrotic syndrome 6.
- Common adverse events associated with rituximab include infusion reactions, susceptibility to infections, and reactivation of viral infections 6, 7.