2023-11-21 23:48:37
The doctor in Chemical Sciences and director of the Immunology laboratory, of the Institute of Biology and Experimental Medicine, dependent on Conicet, is one of the most prominent scientists of the decade. His studies have managed to identify and reveal the function of galectins, proteins of the cells of the immune system and their role in the development of cancer and autoimmune diseases. Recent Konex Brillante Award, he has just announced the launch of Galtec, a public-private biotechnology company that will generate returns to the national State, after 30 years of research.
I would need a brief explanation for beginners of what glycobiology is.
Thank you very much for the invitation, it is a pleasure and a great honor. We work on the borders, at the interface of two disciplines. One is immunology, which is the science that studies our defenses and how our defenses, lymphocytes, which are the central cells and other cells, defend us against different dangers. These dangers can be microbes, but on the other hand, they can also be tumors that are growing. Glycobiology, on the other hand, is the science of sugars. As the word glyco says, it is studying how sugars communicate with different proteins, which recognize these sugars, and how they modulate the function of cells. It is the biology of sugars, as well as different macromolecules such as nucleic acids, DNA, RNA, and proteins are studied, we study carbohydrates. How carbohydrates signal in some way when they are on the cell surface, and are encoded by proteins that understand what they are encoding. So, we work at that interface, at those borders, between immunology and glycobiology, with proteins that we have been working on for thirty years, which are called galectins. Galectins are precisely proteins that approach the surface of a lymphocyte, or other cells, but lymphocytes are the cells of our immune system, they decode information and tell that lymphocyte what to do, if it has to die, proliferate, live, defend ourselves or have to stop those defenses. So, in a way this is what we started working on thirty years ago, through a discovery, I would say almost unexpected, a serendipity, where from an antibody that when I was a student, I was working in the Department of Biological Chemistry, generating antibodies and from that, we identified a protein, which today we know is called Galectin 1. What this protein does is eliminate lymphocytes. You will ask me why do we eliminate lymphocytes? What is the physiological meaning of us eliminating lymphocytes? When we have the invasion of a microorganism, a virus, for example, the virus that causes covid, or a tumor that is growing, any threat, we need an army of lymphocytes to be able to eliminate it. But there comes a time when that army of lymphocytes, which we call clones, all the same that are going to defend, has to return to normal, return to homeostasis, because if it does not return to homeostasis and does not return to its normal number, we are in danger of causing damage to our tissues and causing autoimmune diseases. Galectin 1, the protein that we identified in 1993, has that function. That was the physiological function in health that we saw, it is to stop the responses when they become exacerbated and when there is a danger of this causing harm. For example, in rheumatoid arthritis there is a danger of lymphocytes damaging the joints; in multiple sclerosis, which damage the nervous system; in diabetes, which damage the pancreas. What this protein does is, when an immune response has already reached its peak, it returns to normal, so that those lymphocytes do not go crazy and begin to damage our own tissues and cause autoimmunity. This was quite interesting because upon knowing that Galectin 1, this protein that was released from many cell types, was capable of eliminating T lymphocytes, we began to test it in different diseases, on the one hand, cancer and on the other hand, autoimmune diseases. We call this: the case of Dr. Jekyll and Mr. Hyde.
Which is one and which is another?
Galectin 1, one behaves like Mr. Hyde, like the bad guy in cancer, but behaves like the good guy in the movie, like Dr. Jekyll, in autoimmune diseases. In cancer, what we saw is that tumors produce much more Galectin 1 than any normal cell in our body. Since there is so much, when the lymphocytes, which have the instruction to eliminate the tumor, approach the tumor, the tumor immediately begins to produce high levels of this protein Galectin 1, which kills the lymphocytes as a counterattack before the lymphocytes eliminate the tumor. There was a very big enigma in immunology, if we have an immune system that recognizes a tumor as foreign, how can it not eliminate it, why do tumors grow, why do they metastasize, why do they invade new tissues if they are recognized as foreign? , like a microbe. We tried to answer, through our research, this question and we saw that tumors, as they become more invasive, produce more Galectin 1, human tumors, mouse tumors too, in order to eliminate these antitumor defenses before the lymphocytes kill the tumor. There we reason. If we block this protein, we could open the barriers for the army of lymphocytes to arrive and eliminate the tumor. And that’s what happened. We eliminate Galectin 1 from the tumor microenvironment, using different strategies. First genetics and now also monoclonal antibodies, and we get that army of lymphocytes to reach the tumor and eliminate it. Something that also happened to us is that when we blocked this protein, not only did the lymphocytes eliminate the tumor, which was very good, it was the principle of immunotherapy, but we also saw that the number of blood vessels decreased. A tumor is nourished by oxygen and nutrients and, as it grows, it forms new blood vessels so that all that oxygen and all those nutrients can reach it. This is great, because when we block Galectin 1, we leave the tumor without oxygen, without nutrients, and in turn, the lymphocytes can kill it, so we get very excited about the possibility of this becoming a new therapy.
The cure of cancer.
For cancer cure, cancer treatment. And on the other side there is the other side of the coin, because there is Mr. Hyde, and there is Dr. Jekyll, the good guy from the movie. We said that autoimmune diseases are characterized by a large number of lymphocytes that damage tissues. So, we did the opposite reasoning, what happens if in those cases we give more Galectin 1, so that it eliminates those lymphocytes. Thus, we generated a variant of Galectin 1, very stable in inflammatory sites, which eliminates the extra lymphocytes, those that have already fulfilled their function so that they do not cause autoimmunity. We applied it to models of arthritis, multiple sclerosis, multiple models of autoimmune diseases and it worked. Therefore, we now have two possible therapies and two technologies, a monoclonal antibody that neutralizes Galectin 1, blocking it in cancer, and a variant of Galectin 1, for autoimmune diseases.
That led you to create Galtec, with your Ibyme team they launched a technology-based company. What is the company’s mission?
The company’s mission is to translate all the discoveries we made during thirty years and these technologies that we generated, both the monoclonal antibody and this variant, into medicines, into biopharmaceutical products that can give more opportunities to patients. Today, immunotherapy for cancer has generated an enormous revolution compared to ten, twenty years ago.
This idea that there are specific medications for each patient?
Exactly.
Which are worth hundreds of millions of dollars.
Luckily they are now covered, a large part of the population that needs immunotherapy, which are antibodies with molecules other than galectins, has generated a very, very big revolution. Today, 15% or 20% of patients with different tumors, such as skin tumors, melanoma, lung tumors, head tumors, neck tumors, metastatic kidney tumors, or colorectal tumors, benefit from these therapies. However, there are 80%, 75% of patients who do not benefit, so our idea with Galtec is to provide more opportunities so that with antigalectin antibodies, we can complement current immunotherapies. On the other hand, galectin variants, for autoimmune diseases. When we had, at that time, those two technologies, we said: and what do we do with this? We wanted to reach patients. Enough things had happened to me in my life that led me to make the decision that the ultimate goal of a scientist is to benefit humanity and that I wanted to reach patients with this. There were many options, there were possibilities of licensing the technologies to a multinational, possibilities for other people to develop it. My team and I decided to set up a technology-based company that can first transform, with good manufacturing practices, these technologies into medicines to be presented to the most rigorous regulatory authorities, FDA, EMA, Anmat, etc.; and to be able to transform it ourselves, to do that exercise ourselves.
Specifically, in the United States, in Europe, as well as Argentina.
Exactly. I firmly believe that Argentine science is not only capable of importing or bringing technologies from outside to be able to apply them, or knowledge from outside, but also of generating new knowledge that can be a lighthouse, that can illuminate and transform into new therapies, that is a bit the function of Galtec.
What is the issue of patents, the work they have done, intellectual property, how is it managed by Conicet, how does a public and private company work?
In reality, this company is private, they licensed the patents to us, both Conicet and a non-profit foundation, Fundación Sales, for cancer, have supported every time we had a significant discovery, and that we were able to not only publish it, but before , patent it. It is important to patent to take care of intellectual property before, I knew absolutely nothing about this, they convinced us that it was important to do so and now I am grateful. But, basically we presented the patents, Conicet and the Sales Foundation maintained them over time, since they were approved in different countries around the world, we have the intellectual property of this in different countries around the world. And now that Conicet has licensed the patent to us through a very interesting agreement, in which we commit to the milestones to be met, to return to Conicet the money that supported us so much, with scholarships, with salaries, supporting our project. and taking it forward.
All the money that Conicet invested in you, you are going to return it, would that be the concept?
That would be the concept, the return. We believe in that, that is the way in which international universities do things and work, the idea is to accompany the products as much as we can. There will come a time when we probably have to let them go, but until we reach phase one, phase two. Now we have the private support of a group of Argentine investors, White Lion, we are very happy because they bet on us.
Listen to the full interview on Radio Perfil.
by Jorge Fontevecchia
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