MONOCLONAL ANTIBODIES derived from single clone of antibody producing plasma cells present in the Bone marrow, are very specific to the target such as spike proteins of SARS COV 2 and are free from impurities. They are single dose one time therapy given early in the course of the virus growth and multiplication in the body,before it stimulates immune dis - regulation and set up much feared ‘cytokine storm ‘. Available monoclonal antibodies such as
Regenoron (Roche Cipla) molecule and now Eli Lilly have got the approval for its use in India . Regenoron molecule at the present costs under sixty thousand rupees. It should be given within first seven to ten days of COVID 19 illness specially in cases where there are significant co-morbidities such as obesity, organ failure or uncontrolled complicated diabetes and in whom neutralising antibodies against SARS COV 2 are not formed yet.
Several reports from USA and Europe find it a very useful molecule and within a week it has found users in our country which is purported to preempt costly hospitalisation and subsequent unwanted sequels.
What is antigen and antibody?
What is monoclonal antibody?
Antigens are substances generally a protein, which may also be a complex sugar, lipid or even nucleic acid . VACCINE IS AN EXAMPLE OF ANTIGEN ! It may come from outside or are produced within the body and has specific sites in it to bind to antibodies. These binding sites are known as ‘Epitopes’ . In response to the entry of antigen the body produces antibodies or immunoglobulins . These are Y shaped proteins and have sites to bind to the antigens . These binding sites are known as ‘Paratope’. Antibodies are either polyclonal or monoclonal depending on the numbers of clones. Polyclonal antibodies contain a heterologous mixture of antibodies.
Monoclonal antibody refers to homologous (similar) population of antibodies produced by single clone of plasma cells. These antibodies interact with single epitope of antigen. Therefore it is of high specificity.
It was on 7th August 1975 , ‘Nature ‘ , one of the foremost scientific journal , published a three page report by Dr Cesar Milstein and George J. Kohler describing a method for generating large amounts of monoclonal antibodies of a predefined specificity. It not only revolutionised the biomedical research and diagnostics, it also led to the generation of a whole range of therapeutic arsenals to combat many more diseases including deadly cancer and autoimmune diseases . It is also being used in many diagnostic tools bringing speed and accuracy. Drs Cesar Milstein and George kohler shared the prestigious Nobel prize in physiology or Medicine in the year 1984 for the discovery of Monoclonal antibodies.
The story of this molecule began with the arrival of the Argentinian emigre, Cesar Milstein in 1963 at Molecular Research council Laboratory at Cambridge, UK. He was working for Dr Fred Sanger’s laboratory dealing with molecular biology research , particularly for isolation and purification of single antibody from amongst the billions produced within the body.
Henry Kunkel of Rockefeller institute, New York, way back in 1951 , had noted that Myeloma cells ( cancerous plasma cells of Bone marrow origin ) produce cells nonstop . Kohler and Milstein conceptualised a Hybridoma , a hybrid of two cells of which one is continuously dividing myeloma cells and other an antibody of single clone ie Monoclonal antibody ! This monoclonal antibody was first prepared by injecting the sheep red blood cells into mice spleenic lymphoid tissue (which had natural capacity to produce antibodies). Thus such a monoclonal antibody cell when attached to continuously dividing myeloma cells the attached monoclonal antibody also multiply in numbers and produce immortal monoclonal antibody cell line against sheep red cells . Later on in place of red blood cells of sheep desired antigens were injected in the lymphoid tissue of mice spleen to generate antibodies from mice spleen to be attached to the immortal Myeloma cells to produce unlimited amount of desired monoclonal antibodies.
Recently tremendous advances have taken place in the field of monoclonal antibody generation. We have incorporated the recombinant technology used for production of proteins to produce monoclonal antibodies and PCR (polymerase chain Reaction) technology in place of myeloma cells to scale the output of antibodies many folds. This turned out to be faster technology with greater purity of the generated monoclonal antibodies, however it is costlier and needs a higher skill level than hybridoma technique. In the last decade these antibodies are increasingly being used in difficult to treat Cancers such as Alemtuzumab in chronic lymphatic Leukaemia checkpoint inhibitors in skin cancers and by blocking antibodies in breast and stomach cancers . Apparently these monoclonal antibodies have great potential in modern medicine and newer areas are opening up almost regularly.
The author is former Professor and Head of Medicine, RIMS, Ranchi Jharkhand.