The creator of CAR-T therapies, Carl H. June (New York, 72 years old), believes that we live a process of change in medicine that will lead to a personalized genetic therapies to cure from diabetes to chronic infections or autoimmune diseases. Some of these achievements are relatively close, but there are probably decades to generalize them, even in cancer, which is the scope in which they have begun to function genetically modifying the patient’s immune system T cells and then infused them again and fighting from within against the tumor. The winner of the International Prize for Medical Sciences Doctor Juan Abarca, Abarca Prize, last year, in recognition for his “research and pioneer development of a revolutionary strategy to treat blood cancers based on cell engineering”, attends El País from Pennsylvania (United States) by videoconference.
Ask. CAR-T work in blood cancers, what are the obstacles to extend their success to solid tumors?
Answer. In 2024 there have been many advances in solid tumors. The most prominent was in brain cancer. Three groups in the United States reported adults with refractory glioblastoma, which is the most common brain cancer in adults. We did the first essay in 2015, and this is already the third. In the first two we did not get any response. In those trials, what we did was infuse cells in the blood, such as a transfusion. But now, the three groups that I mentioned manage the cells directly in the brain through a catheter that places the neurosurgeon. We have also introduced other improvements in Car cells, for example, the double direction, that is, that simultaneously attack two tumor molecules instead of one, as we did before, which reduces the possibility of the escape tumor. If only a center had had positive results, we might think it was luck, but the fact that the three have achieved something indicates that it is a good advance for the field. In addition, there have been very important advances in pediatric brain tumors. Currently, there are more than a thousand trials in the world with CAR-T cells, and in preclinical models with mice, new variants of these cells are being tested in practically all types of cancer that can be imagined. The real issue is how long will take these tests in early stages with patients, so that we can have car-t therapies in almost all areas.
P. An oncologist told me that we continue to treat most of the cancers with therapies of the twentieth century, referring to chemo and radiotherapy. when will this change you mention, perhaps in 20 or 30 years?
R. I believe that in less than a decade we will have CAR-T cells for brain cancer. When I was in Spain last year, we established a collaboration between my group, the University and the HM hospitals in Madrid. They have very specialized technologies that allow, for example, to cross the blood brain barrier-which prevents the passage of many therapies to the brain-and that seems very promising to combine it with the CAR-T. I am optimistic. As you said, the main issue is that we don’t know how long it will take.
P. Innovative treatments such as CAR-T are used today especially as a second or third line, when others have failed. When do you think we could start seeing them as first -line treatments?
R. Our first patients arrived when there was no other option, it was the last treatment option. Now they are starting to be used in the second line. I believe that the first place where they will be used as the front line will be in children, because the long -term side effects of chemotherapy are more serious than in adults. Many of them, 20 years later, suffer secondary complications such as other types of cancer, heart damage, and also affects their physical and mental development: their growth slows down and its intellectual quotient is less than if they had not received chemotherapy or radiotherapy. That is why there are already clinical trials in children with leukemia to administer CAR-T cells from the beginning and avoid having to go through years of treatment.
P. To get to that, an economic barrier must also be saved, now the CAR-T are very expensive.
R. Yes, it’s true, but there is a saying in English: death by a thousand cuts [muerte por mil cortes]. The therapy we use, for example, for leukemia, with three years of chemotherapy, all hospital visits and the time when parents cannot work … All that ends up costing a million dollars. In Spain, in addition, you have a very efficient system to administer car-t cells produced in academic centers, and that slights costs. I remember when the first mobile phones came out: only the rich could have one. And now they are much cheaper and also much better. I think the same is happening with cell therapies: there is a lot of work to reduce their price and democratize them, not only for rich countries. But yes, it is still a big problem. There are practically no car-t therapies in the southern hemisphere, except in Australia. They have to get cheaper.
P. With the CAR-T there can also be risks. What side effects are observing?
R. The first CAR-T cells were administered in AIDS patients, with HIV infection. That was something we started to do in 1997. And now almost 20 years have passed since these patients received the cells, and some of them still have them in their body, without having had side effects. There are two types. The first occur in the two weeks after infusion: cytokine release syndrome and, in a subset of patients, neurological effects on the central nervous system. It is reversible, and doctors already know how to handle it effectively. Then there are the long -term effects, related to genetically modified cells that remain in the body. It is still too early to know the long -term risk. But, for now, all experts agree that the risks of CAR-T are much lower than those of chemio or radiotherapy.
P. Beyond cancer, the use of CAR-T is also being explored in other diseases, for example autoimmune.
R. Yes, it has been an amazing finding. He started in Germany, in an academic essay. They used the same CAR that we developed for leukemia and treated an 18 -year -old patient with very refractory lupus. He was taking many drugs due to the side effects of autoimmune disease. And came into full remission. There are more than 80 clinical trials in progress using CAR-T for many autoimmune diseases: lupus, myositis, sclerodermia, multiple sclerosis … Many. And I am quite sure that we will see the approval of this therapy by the drug agency in the United States in two or three years. The first application has been cancer, but it will spread to many others: regenerative medicine, chronic infections such as HIV, and autoimmune diseases. Even things like diabetes. It will be possible that people do not have to take insulin, thanks to new cells that produce it-the cells of pancreatic islets-protected by cells such as CAR-T, which will prevent the body immune system from destroying them again.
P. Will we see a card-based medicine in the future?
R. Yes, yes, no doubt. It is a new paradigm. The next great advance in medicine is cell therapies. It is a very exciting moment.
P. Are there still regulatory barriers to develop CAR-T?
R. Yes, it’s slow. That is probably the greatest obstacle. As is a new technology, health authorities tend to be more conservative. Therefore, in China and Australia, approvals are obtained much faster than in the United States. And I think something similar happens in Europe.
P. Do you think Trump’s return to power would be a threat to scientific progress in his country?
R. Unfortunately, yes. It is still early to know with certainty – just 90 days have passed – but the truth is that there have already been very fast cuts in scientific research, especially in the vaccine area. And we need new vaccines. Right now there is a measles epidemic in the United States, something that is easily prevented. And yet, practically all the investigation in this field has stopped.
P. Do you participate in therapies or experiments that could be affected by these policies?
R. Yes. Here, where I work, we develop vaccines based on RNA. Now we have adapted that technology to manufacture CAR-T cells, and some of those clinical trials have been arrested by the Trump administration. I hope it is something transitory.
P. Can that freezing of funds delay medical advances for years?
R. I think that risk is very real. And one of the great mistakes of science is that he has not done enough to educate the public so that he understands that today we live much more and with better health thanks to scientific research of the last 100 years.
P. After the Covid pandemic, do you think that in this aspect we are better or worse than six years ago?
R. Unfortunately, we are not better. We have the case of Robert F. Kennedy Jr., who is now in charge of our entire health system. He argues that vaccines cause autism, something that has been proven false. He believes that vaccines are not safe. So, in reality, we are worse than before the Covid.
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