Espace Presse – Treatment with monoclonal antibodies

What is a therapeutic monoclonal antibody?

Therapeutic monoclonal antibodies are
molecules manufactured in the laboratory to treat diseases. They are almost identical to the antibodies naturally produced by our immune system to fight biological aggression (viruses, bacteria, fungi, foreign cells, etc.). Hence their effectiveness.

Video explanations

ONE
monoclonal antibody produced in the laboratory acts much like a natural man-made antibody: it specifically recognizes a certain element of the aggressor, called
antigen (for example, a region of a surface protein of a virus) and will bind to it. This antibody-antigen bond will initiate the destruction of the aggressor or prevent it from multiplying.

The specificity of treatments based on monoclonal antibodies lies in their
the ability to hit a target (a protein involved in a disease, a virus, etc.) with very high precision, ranking them among the modern medicine’s most powerful tools.

That
therapeutic monoclonal antibodies has been around for more than thirty years. But it is the arrival of the so-called antibodies
humanized (meaning genetically modified so as not to be rejected by the body) in the late 1990s, which really launched their use. Saw it today
more than a hundred molecules are marketed worldwide, including about thirty in France.

Nobel prizes for monoclonal antibodies

  • 1984 (medicine) : Niels K. Jerne, Georges JF Köhler and César Milstein, for the discovery of the principle of production of monoclonal antibodies
  • 2018 (medicine) : James P. Allison and Tasuku Honjo, for the discovery of cancer treatment with monoclonal antibodies (immunotherapy)
  • 2018 (chemistry) : Gregory P. Winter, for the invention of the Phage display technique, which enables the production of new monoclonal antibodies using viruses.

Which diseases can be treated with monoclonal antibodies?

That
chronic inflammatory diseases,
autoimmune for most of them (Crohn’s disease, rheumatoid arthritis, psoriasis, etc.), so
transplants organs, were the first to benefit from advances in monoclonal antibodies. And in the last ten years, these new therapies have revolutionized the fieldoncology. They are much more targeted and tolerated than chemotherapy, and they have actually changed the management of certain cancers that are considered incurable.

Today, new applications are emerging, such as antibodies
anti-migraineor others who regulate
cholesterol. With
COVID-19is only the second time that monoclonal antibodies against infectious diseases have been developed.

How does a monoclonal antibody work?

Depending on the target targeted, a therapeutic monoclonal antibody can work in different ways:

  • Block a process : by neutralizing molecules such as a surface protein of a virus or a protein involved in an inflammatory disease, it is possible to reduce or even block the development of the pathology in question
  • Destroy target cells : the antibody-antigen bond (example: a receptor expressed on the surface of a tumor cell) can also directly lead to the destruction of the cell
  • Stimulate a biological function : Cancer cells express proteins on their surface that prevent the immune system from recognizing them (immune checkpoints). By targeting and blocking these checkpoints, monoclonal antibodies will strongly reactivate the immune response, leading to the destruction of tumors.

How monoclonal antibodies work © Les Défis du CEA / J. Perrodeau

How do you make a monoclonal antibody?

An antibody is a
very large molecule, impossible to produce by chemical synthesis as for pharmaceuticals. The idea is therefore to have it produced by a living organism.

  • Selection of antibodies, then corresponding genes
  1. In vivo : blood cells from animals (usually mice) are confronted with the antigen and will produce antibodies. The gene that allows the production of the best antibody is then extracted and must then be
    humanized ». Blood cells from healthy patients can also be used.
  2. Or
    in vitro : random banks of antibody genes are artificially created. These genes are “stored” in organisms such as yeast or phages (a very simple variant of virus).
  • Production : the gene for the selected monoclonal antibody is inserted into mammalian cells, selected for their ability to produce large amounts of antibodies. These mini-factories are grown in a bioreactor.

Genetic engineering

When a monoclonal antibody is produced in mice, it must first be ” humanized by replacing certain mouse DNA sequences with human DNA sequences. Thus modified, the antibody injected into the patient will not be considered a foreign body and therefore eliminated.

CEA works on monoclonal antibodies

Several teams are developing monoclonal antibodies that are used as
diagnostic tools new infectious agents and the terrorist threat (NRBC). They are also working on the development of therapeutic monoclonal antibodies, especially for
combating infectious diseases (Covid-19, Ebola…). Three start-up companies from CEA-Joliot have entered the field: Skymab Biotherapeutics Deeptope and Blue Bees Therapeutics.

National research programme

Therapeutic monoclonal antibodies are part of
“Biotherapies and bioproduction of innovative therapies” acceleration strategy launched by the government on January 7, 2022, whose aim is to produce more biomedicine in France against cancer and chronic diseases and to create the medical devices of tomorrow. This strategy is based on a research component called PEPR (Priority Research Program and Equipment), piloted by ANR and handed over to Inserm and CEA.

This article is taken from Défis du CEA No. 250



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Monoclonal antibodies © The challenges of CEA / J. Perrodeau

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