MADRID.— The immunologist Corina Love When he was only 27, he submitted a groundbreaking doctoral thesis that an experimental therapy to eliminate the cells responsible for aging and cancer. In youth, the human body’s defenses are able to destroy these damaged cells, called senescent cells, but as life progresses, the immune system can no longer cope and they accumulate. Amor’s team, led by American biologist Scott Lowe, devised a strategy to extract white blood cells – T cells – from the patient and reorganize them in the laboratory to destroy senescent cells. His proof of concept, in mice, was published two years ago in the magazine Natureshowcase of the best of world science.
Love, born in Madrid 29 years ago, has just inaugurated its own research group, the Amor Lab, at the prestigious Cold Spring Harbor Laboratory in New York City, taking advantage of a program for extremely promising young scientists. Modified T cells, called CAR-Ts, are already used successfully in certain lymphomas and leukaemias, but Amor’s team was the first to show that they could be transformed to eliminate senescent cells. The young immunologist traveled to Madrid this week to give a lecture at the National Cancer Research Center (CNIO).
—Some therapies to eliminate senescent cells with drugs have already been successful in increasing the lifespan of mice.
— Yes, we saw for the first time in genetically modified mice that, if we eliminated their senescent cells, they lived longer. There has been a lot of interest in trying to replicate these results with drugs that could be given to humans. One of the first studies was done with drugs called dasatinib and quercetin and improvement was seen [vivían un 36% más]. We wanted to know if our CAR-T cells could do the same. And we’ve seen big improvements in aging.
“Did they get a lifespan increase?”
“We’ve seen some increase in lifespan, but mostly healthy lifespan. For example, metabolically, these mice have much better glucose tolerance. As you age, you develop diabetes from type 2, but not these mice. And they are in better physical condition.
—The director of the CNIO, María Blasco, wrote with the journalist Mónica Salomone a book entitled Die young, at 140. They commented that the oldest animal in the world is an Iceland clam which lived 507 years. If a clam can, why can’t humans? Can we control aging with therapies targeting senescent cells?
“I think we’re going to see a lot of improvements in terms of the quality of life that we have, until a much older age. But I don’t think we’re going to significantly extend the maximum lifespan we have as a species.
“Why are you so pessimistic?
“I think life expectancy is determined at the genetic level. I would be satisfied if we could live to be 100 with good quality, being well, going out every day, being independent. That would seem to me to be quite a big step forward.
— In the book, it is mentioned that a rat lives three years and a squirrel lives 25 years. This suggests that the rat could live eight times longer with small changes.
—Other groups have created genetically modified animals to eliminate all senescent cells and achieve a longer lifespan, but it’s not brutal. It’s like 10% or 20% more.
“If they eliminate your senescent cells, do you age the same way?”
—You don’t age the same way: you age more slowly and you live longer. But you’re going to die anyway at some point.
“Don’t you believe that the length of human life can be multiplied?
“I think it can be extended, maybe it can be doubled.
— Multiplying the current 80 years by two would be equivalent to living 160 years.
– Stretch a lot. I think 120 or 130 is reasonable.
—Geneticist Ginés Morata claimed that death is not an inevitable biological process, because there are living beings that do not age, such as certain coelenterates.
Yes, but not mammals. Sorry to be so pessimistic. One of the problems I notice in the field of aging is that people tend to stretch it too much. It’s good to be optimistic, and I’m usually very optimistic, but I think it’s more important to focus on what we can actually do, which is improving quality of life and maximizing years. But to say that we will never die…
“When are you going to make the leap to humans?”
“My old hospital, Memorial Sloan Kettering in New York, is trying to start a business, with the goal of doing a clinical trial in two years.
“With what indication?”
“That’s what we decide now. One thinks of hepatic fibrosis induced by non-alcoholic steatohepatitis. It is linked to food, with high fat diets, but it is sometimes irreversible. It is the leading cause of liver transplantation. There is a large affected population.
—Could CAR-T treatment against senescent cells be offered to the general population?
“The problem with CAR-T is that you always have to isolate the cells from the patient and reinject them. It’s a very expensive process, honestly. The holy grail that everyone is looking for is to get a standard treatment, something universal that you can inject into any patient, but it’s difficult.
“Now these complex treatments are being considered for very seriously ill people.
—Yes, in Spain they do CAR-T at the Hospital Clínic in Barcelona, for example, or in La Paz in Madrid, but it is the last option in patients who have already undergone all lines of treatment. This strategy of eliminating senescent cells has potential in certain chronic diseases, such as pulmonary fibrosis, whose patients live as little as a patient with metastatic pancreatic cancer. It is a clinical need, but to generalize these treatments, they would have to be much cheaper, less specific to each patient.
—A few months ago, an experimental therapy with CAR-T developed at the Hospital Clínic de Barcelona achieved complete remission of a cancer, multiple myeloma, in 18 patients with no alternative. Versions of these treatments at private pharmaceutical companies cost around 300,000 euros per person, but the Clinic managed to do it for 90,000.
“Yes, but it’s still a lot.” This is an expensive area. An experiment on mice can cost $10,000 or $20,000.
—One of the problems with CAR-T is that in some patients there is a cytokine storm, an overreaction of the human body’s defenses. Have you detected this phenomenon?
—Yes, we have seen it, but it depends a lot on the dose. We have seen that we can lower the dose and that it is just as effective, without having this toxicity, which is the most frequent in these patients.
—If your CAR-T therapy finally works and produces no adverse effects, what could it be used for?
—For many chronic diseases: hepatic fibrosis, pulmonary fibrosis, diabetes. I think it could have many applications.
“In cancer too?
—Yes, we used it as a therapy, but first inducing tumor cell senescence and then administering CAR-T. That’s what they call the approach one-two shots [en referencia a la combinación de dos puñetazos directos en boxeo, el uno-dos]. We used it on lung cancer in mice and it worked pretty well.
For Manuel Ansede
©El País, SL