At the age of only 27, the immunologist Corina Amor presented a revolutionary doctoral thesis that proposed an experimental therapy to eliminate the cells responsible for aging and cancer.
In youth, the human body's defenses are capable of destroying these damaged cells, called senescent cells, but as life goes on, the immune system cannot cope and they accumulate.
Amor's team, led by American biologist Scott Lowe, devised a strategy to extract white blood cells—T-lymphocytes—from the patient and reengineer them in the laboratory to destroy senescent cells.
Her proof of concept, in mice, was published two years ago in the journal
, a showcase of the best world science.
Amor, born in Madrid 29 years ago, has just opened her own research group, the Amor Lab, at the prestigious Cold Spring Harbor Laboratory in New York, taking advantage of a program for extremely promising young scientists.
Modified T lymphocytes, known as CAR-T, are already used successfully in certain lymphomas and leukemias, but Amor's team was the first to show that they could be transformed to eliminate senescent cells.
The young immunologist visited Madrid this week to give a talk at the National Cancer Research Center (CNIO).
Some therapies to eliminate senescent cells with drugs have already managed to increase the duration of life in mice.
Yes, it was first seen in genetically modified mice that if you removed 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 an improvement was seen [they lived 36% longer].
We wanted to investigate whether our CAR-T cells could do the same thing.
And we've seen some big improvements in aging.
Have you gotten a lifespan increase?
We've seen some increase in lifespan, but mostly healthy lifespan.
For example, on a metabolic level, these mice have much better glucose tolerance.
With age, you develop type 2 diabetes, but these mice don't.
And they are in better physical condition.
The director of the CNIO, María Blasco, wrote a book together with the journalist Mónica Salomone entitled
Dying young, at 140
They commented that the oldest animal in the world is a clam from Iceland that lived 507 years.
If a clam can, why can't humans?
Can aging be controlled with therapies targeting senescent cells?
I think we are going to see a lot of improvement in terms of the quality of life that we have, until a much later age.
But I don't think we're going to greatly extend the maximum lifespan that we have as a species.
I would settle if we can live to be 100 years old being well and going out every day
Why are you so pessimistic?
I believe that life expectancy is determined at the genetic level.
I would be satisfied if we can live up to 100 years with good quality, being well, going out every day, being independent.
That would seem like a pretty significant advance to me.
In the book it was mentioned that a rat lives three years and a squirrel lives 25. This suggests that the rat could live eight times as long with small changes.
Other groups have created genetically modified animals to eliminate all senescent cells and achieve a longer life expectancy, but it is not something brutal.
It's like 10% or 20% more.
If senescent cells are eliminated, do you age the same?
You do not age the same: you age slower and live longer.
But you're going to die anyway at some point.
Do you not believe that the duration of human life can be multiplied?
I think it can be extended, perhaps it is possible to multiply it by two.
Multiplying the current 80 years by two would mean living 160 years.
Stretching a lot.
I think 120 or 130 is reasonable.
The geneticist Ginés Morata has stated that death is not an inevitable biological process, because there are living beings that do not age, such as some coelenterates (a taxon that includes jellyfish, for example).
Yes, but not mammals.
Sorry to be so pessimistic.
One of the issues that I notice in the field of aging is that people tend to stretch it too much.
It's okay to be optimistic and I'm generally very optimistic, but I think it's more important to focus on what we can actually do, which is to increase quality of life and maximize years.
But to say that we are never going to die...
In order to universalize these treatments they would have to be much less expensive
When are you going to make the leap to humans?
My previous hospital, Memorial Sloan Kettering in New York, is trying to start a company, with the goal of doing a clinical trial in two years.
With what indication?
It is what we are deciding now.
We are thinking of non-alcoholic steatohepatitis-induced liver fibrosis.
It is related to food, with diets rich in fat, but sometimes it is irreversible.
It is the leading cause of liver transplantation.
There is a large affected population.
Could CAR-T treatment against senescent cells be offered widely to the population?
The thing with CAR-T is that you always have to isolate the cells from the patient and re-inject them.
It is a very expensive process, honestly.
The grail that everyone is looking for is to get a standard treatment, something universal that you can inject any patient, but it is difficult.
Now these complex treatments are contemplated in people who are very seriously ill.
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, to eliminate senescent cells, has potential in some chronic diseases, such as pulmonary fibrosis, whose patients live as little as a patient with metastatic pancreatic cancer.
It is a clinical need, but in order to universalize these treatments they would have to be much less expensive, not so specific for each patient.
A few months ago, an experimental therapy with CAR-T developed at the Hospital Clínic in Barcelona achieved complete remission of a cancer, multiple myeloma, in 18 patients with no alternative.
The versions of these treatments in private pharmaceutical companies cost about 300,000 euros per person, but the Clínic managed to do it for 90,000.
Yes, but even so it's a lot.
It is an expensive field to work in.
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 saw that we can lower the dose and that it is equally effective, without having that toxicity, which is the most common in these patients.
If your CAR-T therapy ultimately works and has no side effects, what could it be used for?
For many chronic diseases: liver fibrosis, pulmonary fibrosis, diabetes.
I think it could have many applications.
In cancer too?
Yes, we have used it as a therapy, but by first inducing senescence in tumor cells and then giving CAR-T.
It is what they call the
one-two punch approach
[in reference to the combination of two direct punches in boxing, the one-two].
We used it on lung cancer in mice and it worked pretty well.
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