Pharmacology
Summary
Monoclonal antibody therapy involves the use of targeted antibodies, derived from a single cell line, to selectively recognize and neutralize specific disease-causing agents or cells. These humanized and chimeric antibodies are widely utilized today in treatments designed for specific therapeutic targets, such as antigens in cancer cells.
Rituximab, a type of monoclonal antibody therapy, is extensively used as an anti-cancer and immunosuppressive drug (e.g. chronic lymphocytic leukemia (CLL), rheumatoid arthritis, etc.). This chimeric monoclonal IgG targets CD20, a receptor found on the surface of B cells. Through a process called complement-dependent cytotoxicity, rituximab attaches to a B cell and marks it for cell death, resulting in apoptosis.
Other monoclonal antibody therapies like alemtuzumab, bevacizumab, cetuximab, and trastuzumab are also crucial in treating various malignancies. Alemtuzumab, for example, targets CD52 on the surface of B and T cells to treat chronic lymphocytic leukemia, while bevacizumab binds to VEGF and is used to treat metastatic tumors like colorectal cancer and lung cancer. Cetuximab and trastuzumab target EGFR and HER2 receptors, respectively, which are frequently overexpressed in certain types of solid tumors. Side effects for monoclonal antibody therapy include increase risk of infection and progressive multifocal leukoencephalopathy (rituximab), bleeding, thrombotic events, and GI perforation (bevacizumab), papulopustular acneiform rash (cetuximab), and cardiotoxicity (trastuzumab).
Lesson Outline
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FAQs
Rituximab is a chimeric monoclonal antibody that works by binding to the CD20 antigen on B cells, leading to their depletion. This feature is particularly useful in treating conditions characterized by overactive or destructive B cells, such as chronic lymphocytic leukemia (CLL) and rheumatoid arthritis. In CLL, it helps decrease the number of malignant B cells, and in rheumatoid arthritis, it can reduce B cell-mediated inflammation and joint damage.
While monoclonal antibodies are powerful agents in treating certain diseases, they can also lead to several side effects. Both rituximab and cetuximab can cause an infusion reaction, which is characterized by symptoms like headache, fever, skin rash, itching, difficulty breathing, and low blood pressure. In rare cases, chimeric antibodies like rituximab and cetuximab can cause serum sickness, which can present as fever, rash, and joint pain that occurs in the span of 7-10 days. Lastly, rituximab can trigger a higher risk of progressive multifocal leukoencephalopathy (PML), a brain infection, and cetuximab may cause a papulopustular acneiform rash.
Cetuximab, a monoclonal antitumor antibody, functions by binding to the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase. This binding blocks the growth signal, leading to an inhibition of tumor cell proliferation and survival. This effect makes cetuximab beneficial in treating solid tumors such as colorectal cancer and squamous cell carcinoma.
Bevacizumab works against tumor growth by binding to vascular endothelial growth factor (VEGF), inhibiting the formation of new blood vessels within tumors. This lack of a blood supply hampers the growth and spread of tumors. This antibody can be used to treat metastatic tumors like colorectal and lung cancer, and also conditions like wet macular degeneration. However, bevacizumab can lead to side effects such as bleeding, increased risk for thrombotic events, and gastrointestinal perforation.
Trastuzumab is a monoclonal antitumor antibody that specifically targets and binds to human epidermal growth factor receptor 2 (HER2), a receptor tyrosine kinase. By doing this, trastuzumab decreases the proliferation and survival of cancer cells that have elevated levels of HER2, such as in HER2-positive breast cancer. However, it's vital to monitor patients receiving trastuzumab for cardiotoxicity, as it can lead to situations like a diminished left ventricular ejection fraction (LVEF) and heart failure.
