Advances in medicine are seen in every aspect of our lives, from personal health to healing and improving the quality of life for those suffering from various diseases that were once considered incurable. Although medicine has progressed incredibly, there are still many problems and obstacles we face in this modern age. Natural sources are being explored as potential medicine sources and are gaining in importance, both of animal and natural, including marine origins. But what if we go even further and look for a new medicine in one of the most perfectly modified systems in the world – our body?
Antibodies against what bodies?
Antibodies (antibodies) are a natural part of our defence, the immune system. These are glycoproteins that belong to the superfamily of immunoglobulins (Ig) secreted by B lymphocytes, one of the components of our acquired immune system. Their main goal is to neutralize and fight pathogens. They are classified into several classes (IgA, IgD, IgE, IgG, IgM) depending on their heavy chain which is a part of their structure. With their hypervariable region, they bind to the epitopes of the antigen (the parts of the pathogen that it recognizes) and thus perform their function. There are many divisions, but the division into monoclonal and polyclonal antibodies is important to us in this article. The core difference is that monoclonal antibodies are specific for only one epitope of the antigen, while polyclonal antibodies can bind to multiple epitopes. Although both types can be used for different therapeutic purposes, monoclonal antibodies are key for this particular story.
While the synthesis of a classical drug is in some ways fairly simple and direct, the production of monoclonal antibodies is more complicated and must take place in living cells. In 1975, a method for producing monoclonal antibodies for therapeutic purposes was proposed, which involved the fusion of B lymphocytes that have the ability to form antibodies with myeloma cells, thus creating hybridoma cells that divide indefinitely and produce antibodies.
The first ones were created from mouse and rat hybridoma cells, but their success was limited due to their short duration and high immunogenic potential. After that, the approach was changed and attempts were made to “humanize” antibodies, which resulted in chimeric (constant regions are human and variable from rodents), humanized (CDR regions are from rodents, while the rest is a human sequence) to completely human antibodies. MAb (monoclonal antibodies) can be used for pharmacotherapeutic purposes, and are most often of the IgG type (IgG1 is preferred from 4 possible isotypes; IgG1-IgG4).
This type of drug is approved for a wide range of diseases, such as tumours, autoimmune and inflammatory diseases, prevention of transplant rejection… They can be immunotoxic (used to change the pharmacokinetics and pharmacodynamics of soluble ligands), may serve to eliminate target cells, alter cell function, or target delivery of other drugs . One of the disadvantages is the administration of the drug. Due to the metabolism and degradation in the gastrointestinal tract, oral administration is not possible yet. A large number of drugs are administered intravenously while a small portion (adalimumab, certolizumab pegol, efalizumab, omalizumab) can be administered subcutaneously, intramuscularly (palivizumab) or intravitreally (ranibizumab). As this is a foreign protein that is not known to our body, it is not uncommon for the immune system to activate against the taken medicine. Immunogenicity is associated with the percentage of the chimeric portion of the protein, so reactions to human antibodies are much rarer than reactions to the chimeric but not non-existent.
By 2014, 47 such drugs were approved in the U.S. and Europe for a wide range of indications. In 2013, global sales of monoclonal antibodies amounted to nearly $ 75 billion, which is approximately half of the total revenue from biopharmaceuticals. Under new trends, three to five new drugs of this type are approved on an annual basis. Whether we are approaching a new generation of drugs and whether the human body will become an inspiration for the production of new drugs, we are yet to find out …
Translated by: Ines Jurak
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