T-Junction: When Cancer Cells Meet Immune Cells

The last decade has seen great developments in the field of cancer-related immunotherapy. Rather than launch a direct attack with chemotherapy or radiation - which target all body cells, including healthy ones, often leading to serious side effects - doctors encourage the immune system’s T cells, letting it attack the malignant tumor. “T cells are individual immune system cells, whose task is to circulate the body and try to detect alien cells or other adversaries, which is no simple task, as cancer cells are not aliens, they are the body’s own cells that have grown rogue,” says Dr. Alon. “When it works, it’s like magic – the body takes care of itself, with significantly less side effects, which is why immunotherapy is currently used in hospitals across the world. The problem is that for the majority of patients, around 80%, this approach doesn’t work, which makes me ask: why?”

This past decade, Dr. Alon, having joined the Faculty of Engineering about four years ago following a post-doc at MIT, has been actually researching a different subject altogether: He has been looking into the function of synapses in neurons on a molecular level. “Synapses are the connections between neurons. As far as we know, they dictate our ability to learn, which makes them very intriguing for researchers, but physically speaking, these connections are tiny, making them hard to measure on a molecular level,” he explains. “My research over recent years has been focused on RNA molecules, which produce proteins, and I have developed a technology that allows, for the first time, to observe single cells at the RNA and protein level, and thereby measure and study many RNA molecules at the cerebral synapses. For two years now, my students and I have realized that this technology can be used not only in studying the brain, but also for exploring other complex biological questions. For example, it can be used for studying malignant tissue synapses, connecting immune cells and cancer cells.”

As late as ten years ago, it was debated whether the immune system could eradicate cancer cells. Nowadays we know it does eradicate them in most cases, killing cancer cells without us even knowing there was a cancer developing to begin with. However, there are some exceptions: If every encounter between T cells and cancer cells were to end up with the eradication of the cancer cells, there would be no malignant tumors, and even if there were, immunotherapy would have worked, universally. “If we use our technology to look at T cells, and see what happens when they come into contact with single cancer cells, we can learn what happens in this encounter. Can it be that cancer cells change the T cell at the molecular level so as to stop them from reacting, and thereby manage to overcome the body’s defenses? Do they somehow manage to trick them? Does the interaction with a cancer cell make T cells express a particular molecule more strongly, which renders them less responsive to cancel cells? I believe this technology will help us understand why immunotherapy works for some yet not for others, and furthermore, it will later allow us to run this test on a biopsy taken from a specific patient, which may allow doctors to offer them T cells’ manipulation based on the interaction, so that they react differently.”

How exactly is it going to work? “For an interaction to take place between a T cell and a cancer cell, the T cell must physically bind the cancer cell, which they do by means of a receptor found on the cell surface. A high-resolution observation of the interaction between the immune cells and cancer cells will allow us to see and identify these receptors. This can have an actual therapeutic potential, because if we manage to identify the specific receptor that binds cancer cells, it could be synthetically produced in the lab and form the basis for an immunotherapy drug, which could be efficient and personalized.”

The high potential for treating cancer diseases has also been identified by the EU, which has recently awarded Dr. Alon one of its most generous research grants: the ERC Starting Grant. “The grant, about 2 million Euro over five years, is designed to free researchers from mundane financing concerns and allow them to focus on their research. It is awarded to about 200 researchers from all over Europe, which means on average a single researcher from every leading university, across scientific disciplines. This time, Bar Ilan has two grant beneficiaries: Dr. Assaf Ben-Moshe, Department of Chemistry, and myself,” says Dr. Alon. “The EU award the grant to research proposals that they deem groundbreaking, which may sound too obvious: after all, that’s what we do over here at the academy, breaking new ground, right? But as a matter of fact, with most grants it’s the other way around: The greater your research’s chances of success, the greater your chances of securing a grant, which means you’d be more likely to go for stuff you can already pull off. This is what sets ERC apart: They give you money so that you do stuff that’s challenging even for you, with no success guaranteed.”

These days, Dr. Alon’s lab, the spatial genomics lab, is making preparations for the T cell research. “Work on this research actually started two years ago, so that we have initial results to show for, making the EU believe there’s a chance we can pull it off. Now that we’ve received the grant, that’s going to be the lab’s focus,” he says. “At this point, we are successfully watching receptors and starting to sequence then, but there’s still a long way to go before we can fully achieve it, it’s going to take years. I am happy to say that I have a great group by my side, with many excellent students, and I believe we can achieve some groundbreaking results that may allow to pave the way for personalized drugs for different types of cancer.”