Current medicine would not be possible without monoclonal antibodies (և without experimental animals)

One of the allies we had during the epidemic was monoclonal antibodies, some of which were created to detect the virus in diagnostic techniques, and others for therapeutic and preventive use (to neutralize the virus).

In many cases, to obtain them, it was necessary to resort to experimental animal hybridoma technology, which was created more than 45 years ago. Something that contradicts the proposal of the European Commission in 2020, which calls for an end to the use of experimental animals for the development of monoclonal antibodies. As discussed below, we believe that this proposal is premature and could cause significant harm to both research and therapy.

Hybrid cell with “super power”

It was 1975 when researchers Cesar Milstein և Georg Koehler of the Cambridge Medical Research Council published in the journal: Nature: An article that will change immunology forever. Not only that. It has marked many areas of knowledge before and after, especially in medicine.

What was described in the article was a new technique that made it possible to obtain a large number of antibodies against a specific target. That is, a monoclonal antibody.

The technique in question allowed the creation of a new hybrid cell from two others, a specific B lymphocyte և a tumor plasma cell (myeloma). A hybrid cell (or hybridoma) is able to secrete large amounts of antibodies in culture. It can also be grown for a long time, kept frozen and thawed if necessary. All the benefits, in a word.

And what is it for? Well, imagine that we want an antibody that recognizes or neutralizes the SARS-CoV-2 virus. The hybridoma technology procedure involves vaccinating an animal (usually a mouse or rat) several times with virus elements (protein S) to obtain its B lymphocytes (from the spleen, lymph nodes, etc.).

Once extracted, B lymphocytes fuse with myeloma in the laboratory, and the production of the remaining antibodies continues in the laboratory. Thus, several different hybridomas և monoclonal antibodies can be obtained from one animal.

The technique was not patented by the institute where Milstein և Koehler worked, which allowed many research groups to develop and patent their own antibodies (which could be patented individually). Current research in many areas of biomedicine cannot be performed without the help of these monoclonal antibodies.

Multifunctional monoclonal antibodies

In addition, monoclonal antibodies are used in medicine as passive immunizations in disease prevention (for example, virus neutralization), diagnostic methods (quantification of hormones, leukemia ուց tumor study, pathogen detection, prognosis by tumor type, etc.) , interferon …) cleaning. But where they really stand out is in therapy.

In particular, monoclonal antibodies have been used successfully for many years to treat cancer, which is usually combined under the term immunotherapy. They are also useful against autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus or Crohn’s disease. Similarly, monoclonal antibodies have been used against allergies, macular degeneration, hypercholesterolemia, and other “long-term” osteoporosis diseases.

Today there are more than 500 authorized monoclonal antibodies in the therapeutic arsenal or in different clinical stages. Many of them have been developed using basic techniques that can be improved through molecular biology and genetic engineering techniques to make them more compatible with humans.

Getting monoclonal antibodies from hybridoma technology has many advantages. If acquired after specific immunizations, the animal itself can improve its response by receiving highly specific, highly specific antibodies. Both of these aspects are important in the activity of antibodies. It does not seem to be enough, it is a simple, relatively inexpensive technique that allows many research groups to do it.

Initially, this requires the cooperation of the Animal Welfare Service for the pre-vaccination process. But then the whole process is done in vitro without requiring more experimental animals. Different models of animals can be used, especially mice and rats, as well as other examples, such as llamas that have the ability to produce smaller antibodies (nanoparticles), hamsters, chickens, etc.

Based on this technique, which is still fully valid and needed by many researchers, alternatives have been developed that are not yet optimal for all applications. These include the use of viruses that infect bacteria (bacteriophages), the creation of phage libraries, human B lymphocytes by donors, or the generation of genetically modified animal models to produce fully human antibodies.

This is not the time to give up experimental animals

It seems indisputable that the technology of creating hybridomas using animal models is more alive than ever without preventing the development of alternative methods. However, leaving the emergence of hybrids before the sufficient development and introduction of alternative technologies can cause significant damage in both research and therapy.

This comment is related to the proposal, which, as we have already mentioned, we consider premature, which was launched by the European Commission in May 2020 through the ECVAM Committee (European Information Center for the Approval of Alternative Methods). It reaffirmed the need to continue the use of experimental animals for the development of monoclonal antibodies. And it was through the above-mentioned phage libraries that their offspring were able to obtain monoclonal antibodies for all their uses without the involvement of animals.

Unfortunately, science confirms that we are not in that situation yet. Alternative monoclonal antibodies do not always have the quality, ratio, or variety that can still be obtained through hybridoma techniques from the limited use of animals in the early stages of the protocol.

In addition, access to these alternative technologies is much more difficult, expensive and difficult for most laboratories to access. For all these reasons, the method originally approved by Milstein և Koehler in 1975, the hybridoma technology, is still valid today.

In conclusion, due to the technique of monoclonal antibodies, especially hybridoma, great progress has been made in medicine. It is desirable to be very careful and responsible when approaching the transition from conventional methods to alternative methods, so that we do not miss any of the great benefits of the first.

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