Monoclonal Antibodies (mAbs) are a new achievement in molecular biology, they have quickly found application in the treatment of many diseases, and therapies with their use are showing promising results. It is worth finding out what monoclonal antibodies are and how many diseases they are useful.

Monoclonal antibodies(mAb - Monoclonal AntiBodies) owe their name to a specific origin - they are produced by one line - one clone of B lymphocytes, so they are all identical and bind to the same antigen with the same strength - they have the same affinity for it.

Antibody is a protein produced by B lymphocytes, its task is to fight pathogens that have entered our body.

Antibodies are made when foreign substances are present in the body. This is when B lymphocytes "learn" to produce antibodies against them, and then "remember" the new pathogen to fight it again when they come into contact with it.

These particles fulfill their task by attaching to a specific place on a microorganism, most often on the cell membrane, it is called an antigen.

The pathogen destruction mechanisms are also different:

  • microbes are killed after attaching a large amount of antibodies (coating) because they impair the functioning of the cell membrane
  • attaching the antibody activates the so-called complement system, which directly destroys the pathogen
  • most often binding of an antibody gives a signal to phagocytic cells to "devour" a given microorganism.

Antigens can also be, for example, enzymes, in which case the attachment of the antibody usually causes inactivation. In our body, we have an innumerable number of constantly produced antibodies against countless amounts of antigens, and contact with new ones causes the production of antibodies against them, so this pool is constantly growing.

It should be remembered that each strain of B lymphocytes produces different antibodies that bind to different antigens. The number of B-cell groups is therefore as large as many antigens the body "remembers".

Production of monoclonal antibodies

For the production of such antibodies, it is necessary to have a B cell, which produces specific antibodies against the target antigen. From wheredo you take such lymphocytes?

They are taken from mice that have been vaccinated with a predetermined antigen and have produced antibodies against it.

This mouse lymphocyte then binds to the myeloma cell, it is a cancer cell that has the ability to constantly divide, it is said to be immortal.

This fusion creates a hybrid cell, which divides into many B lymphocytes, and the antibodies produced by them bind only to the antigen against which the primary B lymphocyte produced them.

Then the hybridomas, the products of cell connection, are separated from the rest and stimulated to produce antibodies. The latter are isolated and placed in separate vessels to obtain monoclonal antibodies.

In the course of production they can be modified in various ways in order to synthesize:

  • immunotoxins- these are combinations of antibodies with plant or bacterial toxins, thanks to which, when attached, the toxin destroys the cell to which the complex has attached
  • antibodies with drugs- in this way the drug is delivered directly to the damaged area, it allows, for example, to reduce the occurrence of side effects of drugs and to maximize the concentration of the drug in the target area
  • antibodies with isotopes- such fusions allow "irradiation" of neoplastic cells with minimization of side effects and damage to he althy cells
  • chimeric and humanized antibodies- in these, in turn, the murine antibody protein has been replaced to a different extent by human, which reduces exposure to foreign species proteins and the risk of severe allergic reactions ( including shock), which were a great limitation in the use of this therapy
  • abzymów -these are antibodies that act as catalysts, i.e. they accelerate or enable the occurrence of a chemical reaction

The possibilities of modification are therefore very large, they facilitate the action of antibodies not only on the surface of the cell, but also inside it, what is more, the production process enables the production of antibodies against virtually any particles.

At the same time, monoclonal antibodies are very precise molecules, they bind to only one specific structure, their specificity and the multitude of modifications translates into their numerous applications in medicine, not only for treatment.

Monoclonal antibodies in oncology

The best known and widest use of these particles is in the treatment of cancer, mainly because they enable the destruction of specificcells.

However, the condition is the presence of antigens on cancer cells, to which the antibody can attach and initiate destruction.

These antigens must be unique and appear only on tumor cells, because their presence in he althy tissues will cause their destruction and damage to properly functioning organs.

The name of the treatment with monoclonal antibodies is not surprising - it is a targeted therapy, because it allows you to carefully plan the place of action of the drug and the destruction of specific cells.

On the other hand, the uniqueness of antigens is a limitation - this therapy cannot be used in every type of cancer - not all of them have specific antigens or they have not been discovered yet, and those that do, often change their structure over time the duration of the disease.

The variability of neoplasms is so large that even in the case of cancer of one organ, not all patients will have the same antigens, so not everyone will be able to use monoclonal antibodies.

Antibodies work in different ways to treat cancer:

  • trigger immune mechanisms to destroy cancer cells
  • intensify apoptosis, i.e. program cell death
  • block the development of blood vessels in the tumor
  • block growth factor receptors
  • deliver drugs or radioactive elements to cells

In which disease entities is targeted therapy used?

Monoclonal antibodies are most often used in leukemias and lymphomas, e.g. in chronic myeloid leukemia - imatinib, dasatinib, i.e. inhibitors of tyrosine kinases, an enzyme responsible for the regulation of cell division.

In chronic lymphocytic leukemia and in lymphomas - rituximab binds to the CD20 antigen on B lymphocytes.

It is found on "sick" and on he althy lymphocytes, as a result of rituximab therapy all B lymphocytes are destroyed, but their bone marrow precursors do not have the CD20 receptor, therefore they remain undamaged.

After treatment, these cells restore normal lymphocytes.

Also monoclonal antibodies are used in solid tumors, e.g. trastuzumab in breast cancer (it binds to the HER2 antigen) or bevacizumab in colorectal cancer, this antibody in turn combines with VEGF, inhibiting the development of blood vessels in the tumor .

Important

Monoclonal antibodies are also used in transplantology

After organ transplantit is imperative to suppress the immune response that causes organ rejection. It happens that only a specific group of leukocytes attacks a new organ, then it is possible, after their identification, to administer antibodies that inhibit this activity, the remaining white blood cells will still fulfill their task of protecting against infections.

Monoclonal antibodies and autoimmune diseases

Monoclonal antibodies are also widely used in inflammatory diseases, with autoimmune diseases, in this case they are so-called biological drugs, intended for the treatment of e.g. rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis.

Monoclonal antibodies are also used in the treatment of skin diseases - psoriasis or intestinal diseases - Crohn's disease and ulcerative colitis.

All these diseases rely on the inappropriate activation of the immune system, and the implementation of biological treatment allows you to suppress exactly this process in the immune response that is responsible for the occurrence of the disease.

In these diseases, drugs such as adalimumab, anakinra, etanercept are used. Cardiology is another field that uses the achievements of molecular biology.

Monoclonal antibodies: other uses

Abciximab is an antibody that blocks the ability to aggregate platelets, this drug may be a component of the therapy implemented after coronary artery angioplasty, it is still not very popular, but its presence is increasing.

Treatment of poisoning and neutralization of bacterial toxins, e.g. tetanus, is also carried out with the use of monoclonal antibodies, which, by combining with a harmful substance, block its action.

Similarly, in the treatment of osteoporosis, antibodies can be used, one of the methods of treatment is administration of an antibody denosumab, which blocks the activity of osteoclasts - cells responsible for the breakdown of bone.

Monoclonal antibodies in laboratory diagnostics

In addition to a wide range of drugs based on the action of antibodies, also laboratory diagnostics in ELISA and RIA tests uses monoclonal antibodies.

They are used mainly for the diagnosis of infectious diseases and enable the detection of antibodies against the tested pathogen.

Confirmation of the diagnosis of e.g. Lyme disease consists in combining a blood sample with monoclonal antibodies that combine with antibodies developed to fight this disease.

Quite complicated, but the interpretation is a bit simpler - if the reaction does occur, it means that the patient has come into contact withLyme disease and has antibodies to this bacterium, so he was or is sick.

ELISA and RIA tests can also be used to assess the levels of hormones, tumor markers, allergy-related IgE antibodies, and medications.

Monoclonal antibodies: therapy limitations

Monoclonal antibodies are modern preparations, potentially having many benefits and used in a wide range of diseases, yet they are used quite rarely and most often in the most advanced stages of disease. Why?

There are several limitations of their use: firstly, they are quite new drugs and for many we do not know what the long-term effects of their use are and whether they are really safe in the long run.

In addition, monoclonal antibodies can damage he althy cells if they happen to have the same antigen as those being treated.

It is also not uncommon that they cause troublesome side effects, such as nausea and vomiting, diarrhea, but the most dangerous are allergic reactions, including anaphylactic shock.

Unfortunately, this risk will persist as long as a foreign species protein is present in these antibodies (monoclonal antibodies are actually produced by mice).

The last factor is the price, the production process is very complicated and carried out by specialized laboratories.

All this makes the production cost of monoclonal antibodies high - they are the most expensive of all manufactured drugs.

It should also be remembered that monoclonal antibodies are administered only in hospitals due to possible side effects and the need for intravenous use.

So you can't buy them at a pharmacy, not even with a prescription.

Worth knowing

Monoclonal antibodies are the subject of intensive research and the number of available drugs based on them will grow, it remains to be hoped that thanks to them we will be able to fight many diseases more effectively.

Currently, they have a number of applications, although due to the relatively short time of their availability, they are treated like any novelty in medicine, with little reserve.

Unfortunately, monoclonal antibodies also have limitations in use, and sometimes even monoclonal antibodies are not always effective in fighting the disease.

However, it cannot be overestimated that the therapies with their use saved lives or significantly reduced the severity of diseases in many patients with ailments that for many years seemed unstoppable.

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