Argentinian scientists’ breakthrough against cancer could be used for various tumors

For years, the biochemist and doctor in immunology Gabriel Rabinovitch works with proteins Galectin-1 (Gal-1) and after successfully performing a cancer test in human tissue, he announced: “Our work could be extrapolated to other tumor types”. This statement was made during a press conference at Casa Rosada. The next steps, as indicated, will be to deepen the progress of their investigations on this proteinwhich will be tested in the patients.

This Monday, the scientist held a meeting with the Minister of Science, technology and innovation, Daniel Filmus, and the president of the CONICET, Ana Franchi and President Alberto Fernández. “This protein is used by tumors to evade the immune system and form blood vessels. You must take all necessary steps to reach patients with all ethical guidelines of medicine. We started working, at the time, on melanomas – skin tumors – and then we progressed on other tumors such as pancreatic or colorectal tumors, ”says the expert.

In 2014, Rabinovich participated in the publication of work in the scientific journal Cell, in which it was demonstrated in experimental models of cancer that the aforementioned protein served to maintain the tumors in the face of growth blockages encountered in angiogenic therapies. Today, these first steps have become a concrete fact.

“Our work could be extrapolated to other tumor types and, in fact, it has been replicated in other scientific laboratories around the world that have started working with Galectin-1. We are on the right path. We started from a discovery and we must continue in this work which has passed through universities and national centers through CONICET”, warned the scientist. And he pointed out that they were trying to develop “as soon as possible” a drug that increases the immune response to this pathology.

Rabinovich works with Dr. Diego Croci and collaborators at the Rosario Institute of Experimental Biology and Medicine. In their experiments with mice, these researchers were able to block Gal-1 and prevent tumor growth. Seven years later, they were able to confirm the same results in human tissue: this work was published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

In this tone, Rabinovich had previously explained to GlobeLiveMedia“What we detected was that this protein – galectin – was greatly increased in the tumours. We wondered what use it could be for them. And what we saw was that this protein killed our defenses and the lymphocytes disappeared. What was this protein used for that kills the cells that defend our body? Our hypothesis was that it was a tumor escape or counterattack mechanism”.

“Let’s remember that we all have an immune system and that there are cells circulating in our body, called “dendritic cells”, which register the danger and give the order to the lymphocytes to defend us from the viruses which attack us, such as like the flu virus in the lungs or a gastrointestinal virus.Finally, we were able to prove that our hypothesis was correct.When the T lymphocyte – a type of lymphocyte that acts against tumors or viruses – is activated , the tumor begins to activate galectin to kill or paralyze it,” added the specialist.

The work of Rabinovich and his team has shown, using samples from patients with melanoma, that indeed by blocking a protein called Vascular Endothelial Growth Factor (VEGF), Gal-1 can promote angiogenesis by interacting with the VEGFR2 receptor. In turn, the published article presents another relevant scientific novelty: the development of a new human anti-Gal-1 monoclonal antibody which has allowed, in cellular models in vitroinhibit plasma-triggered angiogenesis of cancer patients treated with the anti-angiogenic agent bevacizumab (anti-VEGF).

In this study, led by doctors Nadia Bannoud, Juan Carlos Stupirski and Alejandro Cagnoni, scientists worked with plasma samples from patients with advanced melanoma who participated in a phase III clinical trial. There, the results of bevacizumab administration were put to the test.

The multicenter clinical trial, called AVAST-M, was carried out in the United Kingdom and the 189 samples received by the Argentinian scientists correspond to patients progressively treated with bevacizumab and to the observational group who did not receive said treatment. There were also samples from individuals who had died at the time of analysis.

On this point, Stupirski said: “We received the samples without knowing which group of patients they belonged to and we quantified the amount of Gal-1 that was present in the plasma. It was only after this first stage, and by sending the results to the UK, that we were able to know which group each sample corresponded to and, in the case of those who had been treated with bevacizumab, at which stage of the therapy they matched.

Under these precepts, the experts postulated that the expression of Gal-1 increased not only in patients treated with bevacizumab as the treatment progressed, but also that within this group -not in the group observational- the increase in Gal-1 over time was an indicator of a higher risk of disease recurrence and death.

“These results allowed us to determine that changes in Gal-1 expression in patients treated with an anti-angiogenic agent serve as a biomarker of therapy outcome,” said Rabinovich, director of the IBYME Glycomedicine Laboratory.

Croci, Rabinovich’s colleague on this scientific trip of global importance, recalled: “Although we have not yet carried out clinical trials, in this study we were able to show the development of a new monoclonal antibody to block Gal-1, which can be used in humans. and which it acts to block the pro-angiogenic effects of Gal-1 present in the plasma of patients treated with bevacizumab. Thus, on the one hand, this work confirms the hypothesis, already seen in experimental models, that Gal-1 activates resistance mechanisms against anti-angiogenic therapies and, on the other hand, presents a potential therapy to respond to this issue.” .

“We also show that this process of vessel formation can be inhibited by blocking Gal-1 with a monoclonal antibody developed by the team, which is also presented in this article,” added Nadia Bannoud, another of the authors.

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