Rituximab was first approved by the FDA in 1997 for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma (NHL). Its approval marked a significant milestone in oncology and paved the way for the development of antibody-based therapies. By targeting the CD20 protein on the surface of B cells, rituximab has transformed treatment paradigms for various lymphoproliferative and autoimmune disorders.
Mechanism of Action
Rituximab is a chimeric monoclonal antibody composed of human IgG1 constant regions and murine variable regions that specifically bind to the CD20 antigen. CD20 is a transmembrane protein expressed on B cells from the pre-B cell stage to maturity but is absent on stem cells and plasma cells. Binding of rituximab to CD20 induces B-cell depletion through multiple mechanisms, including:
Antibody-Dependent Cellular Cytotoxicity (ADCC): Recruitment of immune effector cells to destroy CD20-positive cells.
Complement-Dependent Cytotoxicity (CDC): Activation of the complement system leading to B-cell lysis.
Direct Apoptosis: Direct interaction with CD20 triggers programmed cell death.
Antibody-Dependent Phagocytosis (ADP): Enhanced phagocytosis of B cells by macrophages.
These mechanisms collectively contribute to rituximab’s ability to modulate immune responses and treat malignancies and autoimmune diseases.
Indications
1. Non-Hodgkin’s Lymphoma (NHL):
As a monotherapy for relapsed or refractory low-grade NHL.
Maintenance therapy for untreated follicular B-cell NHL.
In combination with chemotherapy for diffuse large B-cell NHL.
2. Chronic Lymphocytic Leukemia (CLL):
Approved alongside fludarabine and cyclophosphamide for newly diagnosed or previously treated CLL.
3. Rheumatoid Arthritis (RA):
Used in combination with methotrexate for adults unresponsive to anti-TNF therapy.
4. Microscopic Polyangiitis (MPA) and Granulomatosis with Polyangiitis (GPA):
Combined with glucocorticoids for these rare autoimmune diseases.
5. Pemphigus Vulgaris (PV):
For adults with moderate-to-severe disease, approved since 2018.
Traditional administration of rituximab involves prolonged intravenous (IV) infusions, requiring careful monitoring for infusion-related reactions. To address this challenge, a subcutaneous formulation combining rituximab with hyaluronidase was approved in 2017. Hyaluronidase increases tissue permeability, enabling faster absorption and reducing administration time to as little as 5–7 minutes.
Biosimilars: Increasing Accessibility and Affordability
The approval of biosimilars such as rituximab-abbs and rituximab-pvvr has widened patient access to monoclonal antibody therapies. These biosimilars have demonstrated equivalence in safety, efficacy, and pharmacokinetics to the original rituximab. Cost reductions associated with biosimilars may alleviate financial burdens on healthcare systems and patients alike, promoting broader usage in both approved and off-label contexts.
Monitoring and Safety
Given its potent effects, rituximab therapy requires rigorous patient monitoring to minimize adverse effects and ensure efficacy. Common side effects include infusion reactions, infections due to immunosuppression, and cytopenias. Long-term use requires vigilance for late-onset complications such as progressive multifocal leukoencephalopathy (PML). Pre-treatment screening for infections, allergies, and other contraindications is critical to mitigate risks.
Healthcare providers must also educate patients and caregivers about the therapeutic goals, potential risks, and management strategies. Open communication fosters adherence and empowers patients in their treatment journey.
Biointron’s catalog products for in vivo research can be found at Abinvivo, where we have a wide range of Benchmark Positive Antibodies, Isotype Negative Antibodies, Anti-Mouse Antibodies, Bispecific Antibodies, and Antibody-Drug Conjugates, including:
