The Magic of  Monoclonal Antibodies 

‘Magic Bullets’ that Kill Cancer

Extreme remedies are most appropriate for extreme diseases.

HIPPOCRATES

. . . the time is coming when there will be magic bullets to treat cancer the way we now treat many infectious diseases with vaccines and antibiotics.

FRANCIS COLLINS

THE news of the award of Nobel Prize for medicine in 1984 to Georges Kohler and Cesar Milstein did not come as a surprise to the scientific community in general. It was, however, felt that the recognition could have come a couple of years earlier, considering the impact the development was expected to have in several fields.

Ever since the famous bacteriologist Paul Ehrlich had dreamt of producing synthetic chemicals to attack micro-organisms such as the dye that was used in combating the parasite causing sleeping sickness, or the arsenic compound that proved effective against syphilis, scientists have been on the look out for an agent that has a comparatively greater range, accuracy and potency.

The breakthrough was finally made about four decades ago when Kohler and Milstein for the first time produced monoclonal antibodies in a laboratory in England’s prestigious Cambridge University, the Mecca of molecular biology. Since then doctors have been using them to tackle a large number of diseases. Some of the areas they have already been proved useful and the fields in which they could be possibly utilized are:

In the treatment of Lymphatic Cancer: Monoclonal antibodies could be used to successfully eliminate the malignant pockets nestling deep in a patient s spleen, liver and lymph modes.

Leukaemia Cells in the bone marrow of a child can be identified and destroyed by injecting monoclonal antibodies.

Tumours can be shrunk in size by using monoclonal antibodies along with radio isotopes.

To eliminate resistance to blood transfusion and detect preliminary signals indicating rejection in kidney transplant cases.

To measure the extent of injury in heart attacks and even check it and indicate the presence of various types of infections.

Attack Foreign Matterp

Monoclonal antibodies are different from the antibodies that the body itself normally produces to combat foreign invaders. A normal antibody has a ‘Y’ shape. It is a protein molecule that can attack any foreign matter, a cell, chemical, bacterium or virus, that enters the human body It is nature’s answer to the invasion of an alien.

Every antibody identifies a specific area or spot on the alien and gets ‘fused’ to it so to speak. When thus identified the alien or‘antigen’ becomes an easy target for obliteration by the entire immune system of a person’s body.

This however is in the nature of an over reaction as even though only one antibody may be required to do the job, a large number of antibodies actually swing into operation. In other words the response developed is far in excess of what is actually required. Monoclonal antibodies are however duplicates of a single cell, specially selected to home in on identified target.

From Mouse’s Spleen

In the laboratory an antigen is injected into a mouse. From the mouse’s spleen, cells capable of making antibodies are taken out. These cells are combined with multiplying ‘myelomas’ (cancer cells in a mouse) and a chemical glue. The product is described as a ‘hybridoma’ which has a dual capability—the capacity of a normal cell to produce antibodies and the ability of the cancer cell to keep on multiplying, thus ensuring an endless supply of antibodies.

The next stage in the process is to separate the hybridomas, get them cloned and decide as to which particular group will produce the antibodies necessary for the battle against a particular antigen. Those that come out successfull in the test are introduced into a mouse to produce more antibodies or developed separately in a laboratory by ‘culturing’. By the use of a centrifugal process, pure monoclonal antibodies are separated from the hybridomas later.

In the beginning  the general trend was to use monoclonal antibody therapy in a judicious manner, combining it with traditional methods such as radiation and chemothrapy. For example in a typical case of leukaemia, drugs could be first administered to remove leukaemia cells that can be seen.The child’s marrow could be then removed and the remaining cancer cells could be eliminated using monoclonal antibodies. 

Since Monoclonal antibodies, or mAbs, are antibodies that have been developed and produced from the same identical parent immune cell, they can be developed and honed by scientists to target and identify specific cells and antigens and to work as antibodies in tandem with the human immune system against them. As research into mAbs and their potential uses is ongoing, scientists hope to augment their knowledge of the antibodies and increase their usefulness. For now, though, here are ten applications of mAbs, some proven and some potential.

Diagnostic Testing.

Once mAbs are produced for a specific substance, they can be then used to test for the presence of that substance in a vessel. This can include toxins, drugs or hormones.

Pregnancy Testing.

MAbs that have been developed to detect human chorionic gonadotropin (HCG) are now present in pregnancy test kits. 

Radioimmunodetection ( RID) of cancer.

An imaging technique used to detect the presence of cancerous or cancer-specific cells has been developed deploying radio-labelled antibodies, which can be produced as mAbs. 

Radioimmunotheraphy (RIT) of Cancer.

Similar to RID, RIT uses mAbs to specifically target antigen cells that are associated with tumours, and then blast these with a lethal dose of radiation, whilst minimising the level of radiation absorbed by normal cells.

Treatment of Cancer through Drugs.

Many different drugs are being developed in clinical trials with the ultimate hope of being able to treat various strains of cancer. In fact, some of these are already on the market. In 1997, a drug named Ritoxin was approved by the FDA for commercial use which is based on mAb technology.

Viral Disease Treatment.

Doctors hope that with further research into mAbs and an increased knowledge of their properties, treatments will become available for diseases previously thought to be incurable, such as AIDS.

Identifying Pathogens.

MAbs can now be used to identify strains of a single pathogen, for example neisseria gonorrhoeae.

Tracing Specific Cells and their Functions.

Scientists can use mAbs to first identify and then track certain cells or molecules in a living thing, and determine its function. For example, scientists at the University of Oregon are using such practices to determine which proteins are responsible for differentiation amongst cells in the respiratory system.?

Organ Rejection.

A certain mAb named OKT3 (developed as an antibody to the T3 antigen) is able to be used to alleviate the effects and likelihood of organ rejection when transplanting new organs into a subject.

Rhesus disease Immunisation.

Anti-rhesus antiserum is becoming increasingly hard to find, and the UK Blood Products laboratory has been researching the possibility of substituting mAb rhesus immunisation, with a view to ultimately replacing the serum.

Thus, it will be seen that the production of monoclonal antibodies forms a milestone in man’s battle against diseases such as cancer, whose pathology and morbidity have defied the onslaught of science till now. It has also ushered in a new age of optimism in which such basic problems as rejection of organ transplant and resistance to blood transfusion would not prove a problem to the surgeon in the operat­ion theatre. In the long-run it may produce as great a revolution in medical science as the discovery of the first group of antibiotics by Alexander Fleming