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Therapeutic antibodies: in the face of cancer, real hope… and a buoyant market – Health


During the annual congress of the American Society of Clinical Oncology (ASCO), at the beginning of June, which brings together the world’s cancer specialists, a study particularly attracted attention: the presentation of a clinical trial on Enhertu, an antibody developed by the Japanese pharmaceutical groups Daiichi Sankyo and the Anglo-Swedish AstraZeneca. This treatment was already authorized in patients suffering from breast cancer with high amounts of a protein called HER2. It has also been shown to be effective in patients with this protein, but in a lower quantity, which therefore increases the number of patients who could benefit from it.

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“An antibody armed with chemotherapy”

Important progress, according to Professor William Jacot, of the Cancer Institute of Montpellier, in the south of France, who participated in this clinical trial. “We had not seen such an advance in terms of survival, with treatment using chemotherapy, for decades,” he says. “It is an antibody armed with chemotherapy: the antibody sticks to the surface of the cancerous cell whose receptors no longer work. The cell then digests the receptors to recycle them: this is where the chemotherapy is released”, explains the oncologist.

The announcements follow one another and also arouse the enthusiasm of investors: recently, the French biotech ImCheck thus raised nearly 100 million euros for an antibody in development. And the big laboratories are not left out, ready to pay dearly. The French Sanofi had thus bought in 2018 the Belgian biotech Ablynx for nearly 4 billion euros, getting its hands on its nanobodies (mini antibodies).

Antibodies made in the laboratory

But how do these antibodies work? It is, in its natural state, an alarm signal, generated by the immune system. Antibodies, which are proteins, recognize substances foreign to the body (called antigens), attach themselves to them and thus signal them to the rest of the immune system. However, in 1975, two scientists, Gerard Köhler and Cesar Milstein, discovered how to produce them in the laboratory, which earned them the Nobel Prize for Medicine. Since then, dozens of synthetic antibodies have been developed. Another advantage of the technology: if its production is complex, it is nevertheless less complicated and expensive to implement than new treatments using cell therapy.

Therapeutic antibodies: how does it work?

The explanations of Jacques Volckmann, head of research and development France of the French laboratory Sanofi

“To understand the origin of antibodies, we have to go back to how our body works. The immune system has specialized cells that produce these large molecules: our antibodies, which are proteins. It is one of the body’s means of defending itself against attacks, bacterial or viral for example. The body sends these small missiles that will block and prevent the spread of a virus, for example.

For about thirty years, we have succeeded in manufacturing specific antibodies in the laboratory. We take the DNA of the desired antibody and clone it into a mammalian cell which will produce it. The improvement of molecular biology technologies has accompanied the development of these techniques. There are many applications in immunotherapy, oncology and infectiology.

In recent years, we can also make multispecific antibodies: they can simultaneously attach to several antigens involved in the disease we want to fight.

Without forgetting the so-called “ADC” antibodies (Antibody Drug Conjugates), the “armed” antibodies. In this case, we develop an antibody that recognizes a specific antigen of a tumor cell, we attach an anti-cancer molecule to it, and the antibody will bring it only where the tumor is. The fields of application are immense. »

In the case of cancer, several modes of action are possible. Therapeutic antibodies will, for example, target the proteins necessary for the production of cancer cells and bind to them to destroy them. Others may act on the regulation of the immune response.

“homing missile”

In recent years, chemotherapy-conjugated antibodies, such as Enhertu, have been added to the panoply. This is also the track developed by the French biotech Inatherys, currently in phase 1 of a clinical trial in leukemia, explains Pierre Launay, director of the company. “Our antibody will bind to the transferrin receptor, a receptor that allows iron to enter the cancerous cell. It is an interesting target because cancer cells need iron. Our strategy is therefore to use a homing missile, which will deliver a poison specifically inside the sick cell to destroy it”, he describes.

In addition to cancers, these treatments are being developed for inflammatory diseases. And even against infections, as for the treatment of patients with covid-19: we can notably cite the Evusheld antibodies from AstraZeneca, used preventively, or, as a curative, Xevudy from the British GSK.

Therapeutic antibodies: why is it expensive?

The explanations of Jacques Volckmann, head of research and development France of the French laboratory Sanofi

“The production of a protein is complex. We start from a DNA sequence, that is to say the genetic code of the protein of the antibody. This sequence is integrated into a mammalian cell, it is cultured and the multiplied cells will then produce the antibody. Then, this antibody is purified, this gives the active raw material.

These are long, expensive and complicated processes, which use very specific and expensive equipment, expensive culture media. All this for relatively low returns. The first productions had a yield of the order of 0.1 gram of antibody per liter of culture. Now, the yield is around 1 g, even 10 g per litre. With the same factory, we produce 100 times more than before. In the next ten years, there will inevitably be improvements in yields. »

With these many potential indications, the market is buoyant: Dupixent, Sanofi’s flagship drug in immunotherapy, thus brought in more than 5 billion euros last year for the laboratory. Keytruda, used in oncology, generated more than 17 billion dollars for the American MSD in 2021. According to estimates by the firm Market data forecast, the global market could reach 249 billion dollars within three years.



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