Prof. Carmit Levy: Immunotherapy has revolutionized cancer treatment," explains Prof. Carmi, "but about 50% of patients do not respond to the standard treatment - the PD-L1 protein. We found a new protein Ly6a against which treatment with an antibody leads to the disappearance of tumors in animals
A technological breakthrough by researchers at the Faculty of Medicine at Tel Aviv University allowed the researchers to discover a new cancer mechanism that prevents the body's immune system from attacking the tumor. The researchers discovered that activation of this mechanism surprisingly succeeds in stimulating the immune system to fight cancer cells, even among cancers that are resistant to standard immunotherapy treatment.
The groundbreaking discovery was led by Prof. Carmit Levy, Prof. Yaron Carmi and PhD student Avishai Malih from the Faculty of Medical and Health Sciences at Tel Aviv University. The results of the study were published in the prestigious journal Nature Communications..
"Everything happened by chance," says Prof. Levy. "I research cancer and also the effect of sunlight/UV, ultraviolet radiation on the skin and body. What these two processes have in common and has been known for many years is that they both suppress the immune system. It is known that sunlight suppresses the skin's immune system and that cancer suppresses the immune system approaching it. The search for mechanisms by which cancer inhibits the immune system excites many researchers all over the world.
We came up with a simple idea that said, let's go out and study what happens with exposure to solar/UV radiation and apply that to what happens in cancer. We knew that when we manage to identify an inhibition mechanism of the immune system, enormous possibilities open up for new treatments."
Prof. Levy adds: "With the idea, I approached my colleague Prof. Yaron Karmi, who is a world expert in the immune system, to join me in the research. At the same time, Avishai Malih began his doctoral work in the laboratory and accepted him to lead the project. The first step was a cross-sectional examination of what changes in the body after exposure to UV radiation. Avishi tested dozens of different proteins and surprisingly and unexpectedly one protein, quite remote, showed a very significant increase following exposure to radiation, this was a very It's surprising, and here we dived deeper to understand what this protein is and why its level increases."
"It is important to explain something very basic about the functioning of the immune system in the body. Our natural immune system is very effective, very powerful, but it contains many brakes and many control stages, all in order for the function to be effective and for the immune system not to act excessively, which will lead to an autoimmune disease, the body attacking itself," Prof. Yaron Karmi explains.
"When our skin is exposed to UV (sun), the immune system is immediately called into action - the blood vessels expand, there are cells with mutations that need to be identified and eliminated and DNA that needs to be repaired where possible. Exposure to UV stimulates the immune system, but of course the body does not want there to be an overreaction - something that could lead to an autoimmune disease. Therefore, after the weakening of the immune system in the skin, a strong control system is activated over the immune system, with the help of lots of brakes."
"Indeed, the use of solar radiation to suppress autoimmune skin diseases has existed for years. That is, for many years doctors have been treating people with autoimmune skin diseases, diseases in which the immune system works excessively in the skin, with UV radiation, because in the end, solar radiation suppresses the skin's immune system," she adds Prof. Levy.
"We discovered that after exposing mice to UV radiation, the T-cells of the immune system, which among other things play a critical role in the fight against cancer, begin to express at high levels a protein called Ly6a. We suspected that this is one of the ways in which UV suppresses the immune system and that the Ly6a protein serves as a" Brax" that can be released and thereby reactivate the immune system optimally" explains Avishai Malih.
"To our surprise, we found out that the same protein, Ly6a, is also overexpressed in cancer, because cancer cells know how to suppress the immune system in a variety of ways, most of which are unknown. When the T cells come into contact with cancer cells, or when they are exposed to UV, This protein that neutralizes them is expressed. We tested the expression in melanoma and colon cancer, and there is no reason to assume that it is different in other types of cancer that we found a general mechanism that allows cancerous tumors to anesthetize the immune system," explains Prof. Carmit Levy.
"What Avishi did was to treat cancer in mice with antibodies against Ly6a, and amazingly the cancer actually regressed. Moreover, a cancer that is resistant to the drugs available today responded significantly to the antibody against Ly6a."
The new discovery may have very practical consequences in the field of immunotherapy - cancer treatment with the help of increasing the response of the immune system.
"Immunotherapy has revolutionized cancer treatment," explains Prof. Karmi, "but about 50% of patients do not respond to the standard treatment - the protein PD-L1. We found a new protein Ly6a, against which treatment with an antibody leads to the disappearance of tumors in our model animals, even in cases of resistance for PD-1. We conducted the research in model animals, and today we are working on translating the research findings into a drug for cancer patients, hoping to bring similar news. to humans".
The find was registered as a patent with the help of Ramot, the commercialization company of Tel Aviv University.
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One response
magnificent!
How many more years will we get to read about such breakthroughs being made in Israel? Not much, mind you.