Scientist Carl H. June (Denver, 1953) remembers his first cases treated with CAR-T twelve years ago, almost as if it were yesterday. One of them was a 65-year-old prison officer with leukemia who had already been given last rites. But a single infusion of the treatment was enough for his cancer to disappear in less than a month. Something similar happened with little six-year-old Emily. It was not a miracle but the fruit of a powerful strategy that today continues to save many patients with leukemias and lymphomas. This treatment consists of extracting T lymphocytes from patients’ blood, modifying them with genetic engineering in the laboratory to multiply their ability to kill cancer cells and injecting them again, as if it were an autotransplant. Hundreds of patients are already considered officially cured thanks to this treatment for which June can be considered her scientific father and for which she always appears in the Nobel Prize in Medicine pools. In Spain yesterday he received the ‘Abarca Prize, an award that recognizes medical findings of international relevance. Oncologists are afraid to talk about curing cancer. Have you already lost that fear? Ten years after treating our first patients, we published in the journal Nature some very sensitive tests where we demonstrated the absence of leukemia and that the CAR-T cells from the treatment continued to work. I think that article marked a milestone, because it showed that CAR-T cells could survive for a long time and were safe. From that moment we could affirm that they were cured. One of those patients is Emily Whitehead who we treated when she was a child. She is now a second year student at the University, without leukemia. Do you still keep in touch with her? Yes, she is a normal, healthy, happy young woman, and I mean, that’s the beauty of it all, that thanks to the treatment Emily can lead a normal life. It is the best you can wish for.Related News standard No Spanish Scientists ‘Snitches’ in the body: They inject nanodiamonds with quantum sensors into cells that warn of pathologies before they appear Standard E.Armora No CAR-T Therapy Miguel Ángel Perales: « I have seen incredible results against cancer» Nuria Ramírez de CastroDo you know how many lives CAR-T treatments have saved? What we know is how many people have been treated. Follow-up for many years is needed to verify that there has not been a relapse. An estimate was published last December that more than 34,000 patients were treated with commercially approved CAR-T cells. They are treatments that pharmaceutical companies have developed, but unlike other drugs, there are universities and hospitals that are manufacturing them within what are called academic trials. At my university we have 20 open clinical trials with new generation cells. So there are more than a thousand open CAR-T trials in the world. No one knows exactly how many people have been treated there, but there are many. It’s probably 50,000 now. You can imagine that I never thought we would reach this volume when we treated our first two patients in 2010. The United States was a pioneer but now the most active country is China. They have given a huge national priority to the development of the next generation of CAR-T cells. Things have changed radically. «We were pioneers but now the most active country is China. They have given an enormous priority to the development of a new generation of CAR-T cells. “In this time you have seen amazing cures, which case has impacted you the most? Well, that is difficult to choose. I remember Bill Ludwig, one of my first cases who was a correctional officer. The treatment freed him from leukemia but he died in 2021 from Covid. Another of my patients has now turned 90 years old and has been able to enjoy his seven grandchildren. His main problem is not leukemia, it is his heart, as happens to so many people his age. At every congress, at every meeting I see patients, some children, who are still alive thanks to the treatment. Just yesterday, at a dinner in Madrid, I sat with a doctor whose father had been treated for myeloma. So therapy is all over the world. Are you still surprised by hopeless cases that you never thought could be cured and go into remission? Yes, all the time, it still surprises me. There is no greater reward than seeing the impact on your research and also the scientific collaboration between countries. I receive visits from Ukrainian scientists who come to talk about CAR-T cells while their country is at war against the Russians. Many scientists who now live in China have been trained in my laboratory… We do not know what may happen with Russia, China and North Korea, but I believe that international science can help. Immunotherapy is a miracle, but it doesn’t always work. In the future, will it be possible to anticipate who will be the best candidates for therapy? Yes. What we know now is that there are different cure rates. In children and young adults we have a 90% complete remission rate for acute leukemia which is truly amazing. But in chronic lymphocytic leukemia, only a third of them are cured. Each tumor has different resistance mechanisms and each patient has a different immune system. In some cases it’s really good, like Olympic athletes. And in others, the immune system is not very good and so it does not work. We are at the point of analyzing all this data to predict what you are asking and solve it. An easy solution is for people with a bad immune system to use the cells of another person who does. Artificial Intelligence will also help us discover why some people respond and others do not. The best results are obtained in leukemias and lymphomas, but not in solid tumors. Why doesn’t it work the same? How can you get around the barrier of breast or pancreatic cancer? Well, that’s a big problem. In blood cancer, CAR-T cells target the bone marrow and reach there very efficiently. There is no access problem. In brain tumors we have tried directly injecting many CAR-T cells and it has worked, however in pancreatic cancer it has not. The cells don’t arrive, it’s like a castle with a moat. And the moat makes it impossible for the CAR-T cell to enter. Cancer always wins. What would be the best strategy for it to work in other tumors? Well, one strategy is to obtain more powerful and safer CAR-T cells and another to combine immunotherapy with antibodies or oncological viruses. We have a very interesting trial at the University of Pennsylvania that is being carried out in collaboration with Barcelona, with the Spanish scientist Ramón Alemany. This is a phase I trial in pancreatic cancer. What does it consist of? An adenovirus is used that is capable of dissolving that moat that protects pancreatic cancer. We have treated six patients with the adenovirus designed in Barcelona and then added treatment with CAR-T. We are obtaining better results than when we give only the cells, so I am very optimistic about the combinations that will be necessary to improve the results in pancreatic cancer. «We seek to rejuvenate the immune system with CAR-T. It is an exciting research project. Do you trust that immunotherapy will also become an anti-aging treatment? One of my students, Daniel Baker, works full time in this area. It seeks to rejuvenate the immune system, although at the moment it only has studies in mice. It is a long way from having a therapy approved by the United States Medicines Agency, but it is an exciting research project. The FDA warned a year ago of the risk that these treatments would cause a new tumor. Was it an unjustified alert? It was a preliminary report and, really, it was a surprise. The conclusion is that patients who have a hematological cancer have a much higher risk of contracting a secondary blood cancer, regardless of the treatment. So there’s data that once you have one blood cancer, you’re five times more likely to get another one. The patients we treat would have died without our therapy. They lived long enough to have what they were meant to have anyway. So it’s probably just wishful thinking. CAR-T cells have nothing to do with that. It has been known for twenty years that chemotherapy causes cancer. This means that 5-10% of women treated with breast or ovarian cancer, even if they are cured, could contract leukemia from chemotherapy. That is never talked about in the press. CAR-T therapy requires isolating the patient’s cells, modifying them, re-infusing them… it is an almost artisanal process, how can the process be made cheaper and faster? That is clearly the most important question. One formula is what is done here, in Spain, with hospitals that develop their own cheaper treatments, the so-called academic CAR-T. At the University of Pennsylvania, each therapy costs us about $50,000; pharmaceutical companies charge $350,000. We do not have the general expenses that they have, nor advertising expenses. Another solution is robotic manufacturing because specialized labor is what makes it most expensive. That’s what’s going to happen in the next decade.
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