Summarizing the two conceptualizations - anibodies are one of the existing mechanisms of the body that are being used to treat and diagnose disease; monoclonal antibodies are like antibodies except they are artificially produced from the clones of a single cell.
In order to understand the actual functionality of these specific antibodies, it is useful to explain the method applied in producing them.
Köhler and Milstein found, in 1975 a way to combine the unlimited growth potential of the myeloma cells with the predetermined antibody specificity of normal immune spleen cells. They did this by literally fusing myeloma cells with antibody-secreting cells from an immunized mouse. The technique is called somatic cell hybridization. The result is a hybridoma.
Hybridoma cells are created by the fusion of two cells in order to combine the distinct characteristics of the two cells into one cell. One of these cells is an antibody producing cell (B-Lymphocyte) from a lab mouse and the other is a tumour of the bone marrow that can be adapted to grow permanently in cell culture, called a myeloma cell. The tumour cells can donate to a normal cell the ability to grow indefinitely and at a rate that exceeds normal cell growth. This means that when hybridoma cells are grown in the lab, they replicate faster than normal antibody producing cells in the body, and the individual hybridomas produce the specific antibodies for an indefinite time period.
A hybridoma will produce the monoclonal antibody that was originally produced by the B-Lymphocyte cell. The kind of antibody the original B-Lymphocyte cell produces depends on the kind of antigen that was injected into the mouse before the B-Lymphocyte cells were harvested. For example, if the mouse was injected with a flu virus, the mouse will have B-Lymphocytes that produce flu antibodies. When fused with a tumour cell to make a hybridoma, the hybridoma will produce monoclonal antibodies against the flu.
After the hybridoma cells are created and chosen for effectiveness in the lab, they are put into media that can help them grow and subsequently produce the monoclonal antibodies. There are two ways of doing this:
- in vitro: that is, in culture vessels. The yield runs from 10-60 µg/ml.
- in vivo: growing in mice. Here the antibody concentration in the serum and other body fluids can reach 1-10 mg/ml.
This product of cell fusion combined the desired qualities of the two different types of cells: the ability to grow continually, and the ability to produce large amounts of pure antibody.
Not only does this provide the basis for protection against disease organisms, but it makes antibodies attractive candidates to target other types of molecules found in the body, such as:
- receptors or other proteins present on the surface of normal cells
- molecules present uniquely on the surface of cancer cells.
But there are problems to be solved before antibodies can be used in human therapy.
One,is the response of the immune system to any antigen, even the simplest, is polyclonal. That is, the system manufactures antibodies of a great range of structures both in their binding regions as well as in their effector regions. Second, even if one were to isolate a single antibody-secreting cell, and place it in culture, it would die out after a few generations because of the limited growth potential of all normal somatic cells.
The main difficulty is that mouse antibodies are "seen" by the human immune system as foreign, and the human patient mounts an immune response against them, producing HAMA ("human anti-mouse antibodies"). These not only cause the therapeutic antibodies to be quickly eliminated from the host, but also form immune complexes that cause damage to the kidneys.
Genetic engineering techniques allow scientists to make "humanized" (almost human) monoclonal antibodies by grafting a human antibody onto a mouse one. Only the portion of the mouse antibody that is critical in binding to a target antigen stays unchanged. Humanized monoclonal antibodies are approximately 90 percent human. This makes them less likely to be rejected by the human body, and more likely to be effective.
When monoclonal antibodies are used in therapy, they are often attached to different drugs or toxins, which are then delivered to the target cells without harming the other cells in the body. In diagnosis, radioactive markers are attached to them to locate a certain kind of cell within the body. They are used in diagnostic imaging of internal organs and tumours.
Because selected hybrid cells produce only one specific antibody, they are more pure than the polyclonal antibodies produced by conventional techniques. They are potentially more effective than conventional drugs in fighting disease, since drugs attack not only the foreign substance but the body's own cells as well, sometimes producing undesirable side effects such as nausea and allergic reactions. Monoclonal antibodies attack the target molecule and only the target molecule, with no or greatly diminished side effects.
What can we conclude from all this? That humans try too hard to perform actions only Mother Nature can do; that we’re missing the main points of a ridiculous research. Or are we supporting our own existence by externally overproducing something our own bodies already have – an immune system? Monoclonal antibodies have brilliant purposes and, if correctly produced, their appliance in modern medicine can revolutionize the treatment of an endless number of deathly diseases. It is only a matter of time for science to develop a more perfect model of our “true selves” and use it to cure Nature’s unsuccessful “DEMO version”.
