What are monoclonal antibodies?
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful antigens such as viruses.
A monoclonal antibody is a type of protein made in the laboratory that can bind to substances in the body, including cancer cells. However, there are many kinds of monoclonal antibodies. Also, a monoclonal antibody is made so that it binds to only one substance.
Monoclonal antibodies are being used to treat some types of cancer. They can be used alone or to carry drugs, toxins, or radioactive substances directly to cancer cells.
How does it works? Monoclonal antibodies
First, the body’s immune system generates antibodies as a defense mechanism against unfamiliar molecules. The scientific term for such unfamiliar molecules is antigens.
Molecules from bacteria and viruses can act as antigens, prompting the production of antibodies.
Antibodies bind to antigens. This tells specialized cells of the immune system to kill the invading pathogen.
Monoclonal antibodies can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody).
In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody secreting plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one monoclonal antibody to two epitopes.
In fact, it is possible to produce monoclonal antibodies that specifically bind to virtually any suitable substance. Besides they can then serve to detect or purify it. This capability has become an important tool in biochemistry, molecular biology, and medicine.
Monoclonal antibody therapy
Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAb) to bind monospecifically to certain cells or proteins.
In addition, the objective is that this treatment will stimulate the patient’s immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes a target cell line, delivering lethal chemical doses.
More recently antibodies have been used to bind to molecules involved in T-cell regulation. This is known as immune checkpoint therapy.
Antibody structure and function
Immunoglobulin G (IgG) antibodies are large heterodimeric molecules, approximately 150 kDa and are composed of two kinds of polypeptide chain, called the heavy (~50kDa) and the light chain (~25kDa).
In addition, the two types of light chains are kappa (κ) and lambda (λ). By cleavage with enzyme papain, the Fab (fragment-antigen binding) part can be separated from the Fc (fragment constant) part of the molecule.
The Fab fragments contain the variable domains, which consist of three antibody hypervariable amino acid domains responsible for the antibody specificity embedded into constant regions.
The four known IgG subclasses are involved in antibody-dependent cellular cytotoxicity.
Antibodies are a key component of the adaptive immune response, playing a central role in both in the recognition of foreign antigens. As well as, the stimulation of an immune response to them.
The advent of monoclonal antibody technology has made it possible to raise antibodies against specific antigens presented on the surfaces of tumors. Monoclonal antibodies can be acquired in the immune system via passive immunity or active immunity.
The advantage of active monoclonal antibody therapy is the fact that the immune system will produce antibodies long-term, with only a short-term drug administration to induce this response.
However, the immune response to certain antigens may be inadequate, especially in the elderly. Additionally, adverse reactions from these antibodies may occur because of long-lasting response to antigens.
Passive monoclonal antibody therapy can ensure consistent antibody concentration, and can control for adverse reactions by stopping administration. However, the repeated administration and consequent higher cost for this therapy are major disadvantages.
Monoclonal antibody therapy can aid the immune system because the innate immune system responds to the environmental factors it encounters by discriminating against foreign cells from cells of the body.
Therefore, tumor cells that are proliferating at high rates, or body cells that are dying which subsequently cause physiological problems are generally not specifically targeted by the immune system, since tumor cells are the patient’s own cells.
Tumor cells, however are highly abnormal, and many display unusual antigens. Some such tumor antigens are inappropriate for the cell type or its environment.
Monoclonal antibodies can target tumor cells or abnormal cells in the body that are recognized as body cells, but are debilitating to one’s health.
Possible side effects of monoclonal antibodies
Monoclonal antibodies are given intravenously (injected into a vein). The antibodies themselves are proteins, so giving them can sometimes cause something like an allergic reaction. This is more common while the drug is first being given. Possible side effects can include:
- Low blood pressure
Compared with chemotherapy drugs, naked mAbs tend to have fewer serious side effects. But they can still cause problems in some people.
Once monoclonal antibodies for a given substance have been produced, they can be used to detect the presence of this substance. Proteins can be detected using the Western blot and immuno dot blot tests. In immunohistochemistry, monoclonal antibodies can be used to detect antigens in fixed tissue sections, and similarly, immunofluorescence can be used to detect a substance in either frozen tissue section or live cells.
Analytic and chemical uses
Monoclonal antibody or rather Antibodies can also be used to purify their target compounds from mixtures, using the method of immunoprecipitation.
Therapeutic monoclonal antibodies act through multiple mechanisms, such as blocking of targeted molecule functions, inducing apoptosis in cells which express the target, or by modulating signalling pathways.
One possible treatment for cancer involves monoclonal antibodies that bind only to cancer-cell-specific antigens and induce an immune response against the target cancer cell.
Such mAbs can be modified for delivery of a toxin, radioisotope, cytokine or other active conjugate or to design bispecific antibodies that can bind with their Fab regions both to target antigen and to a conjugate or effector cell.
Every intact antibody can bind to cell receptors or other proteins with its Fc region.