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The creator of CAR-T therapies – 72-year-old Carl H. June – believes that we’re experiencing a process of change in medicine. And he affirms that this will lead to a system based on personalized gene therapies that will be able to cure everything, from diabetes and chronic infections, to autoimmune diseases.
Some of these breakthroughs are relatively close. However, they will likely take decades to become widespread. In the field of cancer, for instance, these therapies have begun to be utilized to genetically modify the T cells of patients’ immune systems. The T cells are then infused again, so that they can fight tumors from within.
Last year, the New York-born June won the Doctor Juan Abarca International Award for Medical Science, in recognition of his “research and pioneering development of a revolutionary strategy to treat blood cancers, based on cell engineering.” He spoke to EL PAÍS from Pennsylvania via videoconference.
Question: CAR-T cells work in blood cancers. What are the obstacles to extending their success to solid tumors?
Answer: In 2024, there were many advances in solid tumors. The most notable was in brain cancer. Three [study groups] in the United States reported on adults with refractory glioblastoma, which is the most common brain cancer in adults. We conducted the first trial in 2015. [We’re now on] the third.
In the first two, we didn’t get any responses. In those trials, we infused the cells into the blood, like a transfusion. But now, the three groups I mentioned were administered the cells directly into the brain through a catheter placed by the neurosurgeon.
We’ve also made other improvements to CAR-T cells. For example, dual targeting: [this means that] they simultaneously attack two tumor molecules – instead of just one, as we did before – which reduces the chance of the tumor escaping. If only one [research] center had had positive results, we might think it was luck… but the fact that all three achieved something indicates that it’s a good advance for the field.
Additionally, there have been very important advances in pediatric brain tumors. Currently, there are more than a thousand trials involving CAR-T cells worldwide. New variants of these cells are being tested in pre-clinical mouse models in virtually every type of cancer imaginable. The real question is how long it will take to conduct these early-phase trials with patients, so that we can have CAR-T therapies in almost every area.
Q. An oncologist told me that we still treat most cancers with 20th-century therapies, referring to chemotherapy and radiotherapy. When will this shift you mention occur? Perhaps in 20 or 30 years?
A. I believe that, in less than a decade, we’ll have CAR-T cells [to treat] brain cancer. When I was in Spain last year, we established a collaboration between my group, the university and HM Hospitals in Madrid. They have highly specialized technologies that allow, for example, crossing the blood-brain barrier – which prevents many therapies from entering the brain – and this looks very promising for combining [current treatments] with CAR-T cells. I’m optimistic. As you said, the main issue is that we don’t know how long it will take.
Q. Innovative treatments like CAR-T cells are currently used mostly as second- or third-line therapies, after others have failed. When do you think we might start seeing them as first-line treatments?
A. Our first patients arrived [at our center] when there was no other choice; it was the last treatment option. Now, [CAR-T cells are] starting to be used as second-line therapies. I think the first place they’ll be used as first-line therapies will be in children, because the long-term side effects of chemotherapy are more severe [in children] than in adults. Many of them – 20 years later – suffer from secondary complications, such as other types of cancer [and] heart damage. [Chemotherapy] also affects their physical and mental development: their growth slows and their IQ is lower than if they hadn’t received chemotherapy or radiation therapy. That’s why there are already clinical trials in children with leukemia to administer CAR-T cells from the beginning, so as to avoid having to undergo years of treatment.
Q. To achieve this, we also have to overcome a financial barrier: currently, CAR-T cells are very expensive.
A. Yes, that’s true, but there’s a saying: death by a thousand cuts. The therapy we use for leukemia [in children], for example – with three years of chemotherapy, all the hospital visits and the time parents can’t work – all of that ends up costing a million dollars.
In Spain, you have a very efficient system for administering CAR-T cells that are produced in academic centers. This greatly reduces costs. I remember when the first cell phones came out: only the rich could have one. And now, they’re much cheaper… and also much better. I think the same thing is happening with cell therapies: there’s a lot of work to reduce their price and make them more democratic, [so that they’re] not just for rich countries. But yes, it’s still a big problem. There are practically no CAR-T therapies in the southern hemisphere, except in Australia. They need to be made cheaper.
Q. With CAR-T cells, there can also be risks. What side effects are you seeing?
A. The first CAR-T cells were administered to patients with AIDS [and] HIV. That was something we started doing in 1997. And now, it’s been almost 20 years since those patients received the cells… and some of them still have them in their bodies, without having experienced any side effects.
There are two types [of side effects]. The first occur within two weeks after the infusion: cytokine release syndrome, [a systemic inflammatory response]. In a subset of patients, [this causes] neurological effects in the central nervous system. It’s reversible; doctors already know how to manage it effectively. Then, there are the long-term effects, related to the genetically-modified cells that remain in the body. It’s still too early to know the long-term risk. But for now, all experts agree that the risks of CAR-T cells are much lower than those of chemotherapy or radiation therapy.
Q. Beyond cancer, the use of CAR-T cells is also being explored in other diseases. For instance, in autoimmune disorders.
A. Yes, this has been an amazing discovery. It started in Germany, in an academic trial. They used the same CAR-T cell we developed for leukemia and treated an 18-year-old patient with highly refractory lupus. She was taking a lot of drugs due to the side effects of the autoimmune disease. And she went into complete remission.
There are more than 80 clinical trials underway using CAR-T cells for many autoimmune diseases: lupus, myositis, scleroderma, multiple sclerosis… many [diseases]. And I’m pretty sure that we’ll see this therapy approved by the Food and Drug Administration in the United States in two or three years. The first application was [in] cancer, but it’s going to expand to many others: regenerative medicine, chronic infections like HIV, [as well as] autoimmune diseases. Even [chronic conditions] like diabetes. It will be possible for people to not have to take insulin, thanks to new insulin-producing cells – pancreatic islet cells – which are protected by cells like CAR-T cells, which will prevent the body’s immune system from destroying them again.
Q. Will we see CAR-T-based medicine in the future?
A. Yes, yes, definitely. It’s a whole new paradigm. The next big advance in medicine is cell therapies. It’s a very exciting time.
Q. Are there still regulatory barriers to developing CAR-T therapies?
A. Yes, it’s [a slow process]. That’s probably the biggest obstacle. Since it’s a new technology, health authorities tend to be more conservative. That’s why approvals are obtained much faster in China and Australia than in the United States. And I think something similar is happening in Europe as well.
Q. Do you think Trump’s return to power will threaten scientific progress in your country?
A. Unfortunately, yes. It’s still too early to know for sure but the truth is that there have already been very rapid cuts in scientific research, especially in the area of vaccines. And we need new vaccines. There’s a measles epidemic in the United States right now, something that’s easily preventable. And yet, virtually all research in this field has come to a standstill.
Q. Are you involved in therapies or experiments that could be affected by these policies?
A. Yes. Here, where I work, we develop RNA-based vaccines. We’ve now adapted that technology to manufacture CAR-T cells… and some of those clinical trials have been halted by the Trump administration. I hope it’s temporary.
Q. Could this funding freeze delay medical advances by several years?
A. I think that risk is very real. And one of the great mistakes of science is that it hasn’t done enough to educate the public, [so that people can] understand that we’re living much longer and healthier lives today thanks to the scientific research that’s been done over the last 100 years.
Q. After the COVID-19 pandemic, do you think we’re better or worse off in this regard than we were six years ago?
A. Unfortunately, we’re not better off. We have the case of Robert F. Kennedy Jr., who’s now the head of our entire healthcare system. He claims that vaccines cause autism, something that has been proven false. He believes vaccines are unsafe. So, actually, we’re worse off than before COVID.
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