Monoclonal Antibodies "EMPOWER IAS"

News:

• Pharma major Biocon received the approval of the Drugs Controller General of India (DCGI) to market Itolizumab (a monoclonal antibody which is used to treat acute psoriasis) for treatment of cytokine release syndrome (CRS) in moderate to severe acute respiratory distress syndrome patients due to COVID-19.

 

What are monoclonal antibodies?

• Monoclonal antibodies are proteins cloned in the lab to mimic antibodies produced by the immune system to counter infection. They have their genesis in serum, the colourless constituent of blood that contains antibodies.
• These proteins bind to an antigen, the fragment of an infectious virus in the case of SARS-CoV-2, and either destroy it or block its action.
• In the case of COVID-19, there are yet no proven drugs to treat moderate or severe manifestations of the disease. Among the therapies being tested is convalescent plasma, which is a constituent of blood and recovered from those who have successfully fought the disease. This blood contains antibodies produced within a week or two of being infected.
• While plasma therapy involves injecting this entire antibody-soup into another sick patient, a monoclonal antibody can be made by isolating specific antibodies and multiplying them via various techniques.

 

Applications of Monoclonal antibodies: 

• Diagnostic Applications: Monoclonal antibodies have revolutionized the laboratory diagnosis of various diseases. For this purpose, MAbs may be employed as diagnostic reagents for biochemical analysis or as tools for diagnostic imaging of diseases.

1. MAbs in Biochemical Analysis: Diagnostic tests based on the use of MAbs as reagents are routinely used in radioimmunoassay (RIA) and enzyme- linked immunosorbent assays (ELISA) in the laboratory. These assays measure the circulating concentrations of hormones (insulin, human chorionic gonadotropin, growth hormone, progesterone, thyroxine, triiodothyronine, thyroid stimulating hormone, gastrin, renin), and several other tissue and cell products (blood group antigens, blood clotting factors, interferon's, interleukins, histocompatibility antigens, tumor markers).
2. MAbs in Diagnostic Imaging: Radiolabeled—MAbs are used in the diagnostic imaging of diseases, and this technique is referred to as immunoscintigraphy. The radioisotopes commonly used for labeling MAb are iodine—131 and technetium—gg. The MAb tagged with radioisotope are injected intravenously into the patients. These MAbs localize at specific sites (say a tumor) which can be detected by imaging the radioactivity.

• Therapeutic Applications: Monoclonal antibodies have a wide range of therapeutic applications. MAbs are used in the treatment of cancer, transplantation of bone marrow and organs, autoimmune diseases, cardiovascular diseases and infectious diseases. Autoimmune diseases like rheumatoid arthritis and multiple sclerosis are of great concern. Some success has been reported in the clinical trials of rheumatoid arthritis patients by using MAbs directed against T- lymphocytes and B-lymphocytes.
• Protein Purification: Monoclonal antibodies can be produced for any protein. And the so produced MAb can be conveniently used for the purification of the protein against which it was raised. 
• Catalytic MAbs (ABZYMES): Catalysis is the domain of enzymes. The most important common character between enzymes and antibodies is that both are proteins. Further, the binding of an antibody to its antigen is comparable to the binding of an enzyme to its substrate. In both instances, the binding is specific with high affinity and involves weak and non-covalent interactions (electrostatic, hydrogen and van der Waals forces). The striking difference is that the enzyme alters the substrate (to a product) while the antigen bound to antibody remains unaltered.

 

How useful are they in treating COVID-19 patients?

• Experts are not sure why, but have observed that many who died were victims of a cytokine storm — when the immune system goes into overdrive to flush out the virus. Pro-inflammatory cytokines recruit a host of specialised immune system cells to neutralise antigens.
• However, these cytokines can aggravate inflammation and injury in lung cells as well as in several other organs. A challenge in treatment is how to prevent this over-reaction. One method is to use antibodies that can block a particular protein, called CD6. They are found on the surface of T-cells, a class of cells that are a central prong in the body’s defence system.
• Experts say if this CD-6 is suppressed, it will prevent the T-cells from releasing a cytokine cascade and thus better regulate the immune system. There is also a lot of research going on in using such antibodies to prevent the replication of the virus.
• Since last month there have been reports from laboratories from nearly everywhere, reporting the presence of one or more antibodies that could be used to block the ‘spike’ protein, the key the coronavirus uses to infiltrate lung cells and proliferate.
• Before monoclonal antibodies were roped into discussions surrounding COVID-19, research has focused on deriving the right kind of antibodies that specifically bind onto regions of interest. These underpin the design of cancer therapies or fixes for autoimmune diseases.