|
Full Prescribing Information, including Boxed Warnings
The Role of Rituxan® in Non-Hodgkin's Lymphoma
- The immune system is a highly integrated network of cells, tissues, and organs that defends the body against infection and disease. This system can identify and destroy millions of foreign invaders such as bacteria, viruses, fungi and toxins, and also helps to protect the body against the growth of cancerous cells. Specialized cells called white blood cells are part of the immune system. Types of white blood cells include lymphocytes (B-cells and T-cells), and macrophages.
- The lymphatic system is important to the immune system for the production and transportation of lymphocytes throughout the body, and includes a network of specialized circulatory vessels and organized structures known as lymph nodes. Lymph nodes are the sites in which B-cells and T-cells respond to invasion by foreign substances (antigens) and help prevent their spread throughout the body.
- Under some circumstances B-cells and T-cells can malfunction, and this can cause or contribute to the generation of malignant (cancerous) cells. These malignant cells divide uncontrollably and do not fully differentiate. The resultant blood cancers are known as lymphomas, leukemias or myelomas. Non-Hodgkin's lymphoma (NHL) is one type of blood cancer that can arise from abnormal immune cells. About 85% of Non-Hodgkin's lymphomas arise in B-cells. Therefore, an approach to combating NHL is to target B-cells.
- Each mature B-cell is designed to recognize and locate one specific antigen in the body via special structures on its outer surface called B-cell receptors. B-cell receptors fit together with their matching antigen like a lock and key. The binding of an antigen to its matching B-cell receptor is the first step toward the body's production of antibodies. Antibodies are essential to help protect the body against infection and disease. They are Y-shaped proteins that are nearly identical to B-cell receptors, except that they are secreted into the bloodstream instead of remaining attached to a B-cell. Like B-cell receptors, one antibody is specific for one antigen. When an antibody finds its matching antigen, it neutralizes or marks it for destruction.
- In addition to producing antibodies, B-cells exert other important influences on other types of immune cells.
- Abnormally functioning B-cells can lead to or contribute to various diseases.
- Research into specific proteins on B-cells has uncovered evidence that a particular protein, CD20, is expressed on the majority of mature B-cells and not on bone marrow stem cells. Greater than 90% of malignant B-cells in NHL express the CD20 antigen. Although the function of CD20 is not fully understood, data implicate a function for CD20 in regulation of the cell cycle and apoptosis (also known as cellular suicide, or programmed cell death).
- Rituximab is a monoclonal antibody, which means it was designed and made by scientists to target one kind of cell. Rituximab specifically binds to the CD20 antigen on the surface of B-cells. From there, it is believed to work with the body's own immune system to attack and kill the affected B-cells. This approach can be used to target malignant B-cells in patients with NHL. While the exact mechanism is unknown, experimental evidence supports three different mechanisms play a role in the clinical activity of Rituxan. These include:
 |
Antibody-Dependent Cellular Cytotoxicity (ADCC) - ADCC is a process in which specific cells are coated with antibodies and targeted for destruction by specialized killer cells, such as natural killer cells and macrophages. In this situation, one part of the antibody rituximab binds to the CD20 antigen on B-cells. Another part of the same rituximab antibody binds to a receptor on specialized killer cells such as monocytes, macrophages, and natural killer cells. The killer cells then engulf the B-cell and destroy it.
Complement-Dependent Cytotoxicity - In this scenario, the antibody rituximab binds to CD20 on B-cells, and initiates the complement system, also known as the 'complement cascade', leading to direct cell toxicity. The end result is formation of a membrane attack complex that makes a hole within the cell membrane, causing cell lysis and death.
Apoptosis - Experimental evidence has suggested that rituximab attaches to and cross-links the CD20 antigen, activating a cascade of events that ultimately causes B-cells to commit cellular suicide, otherwise known as programmed cell death, or apoptosis.
|
|
