Corina Amor Vegas, an associate professor at Cold Spring Harbor Laboratory, and her research team have made a scientific discovery that could help restore gut health in people suffering from age-related diseases. The work builds on advances in immunotherapy and aging research, and could soon lead to clinical trials aimed at improving the quality of life for patients whose intestinal tissue has been damaged by aging or cancer treatment.
The discovery centers on the intestine, an organ critical to digestion and overall health. Under normal conditions, the intestinal epithelium, a single layer of cells lining the gut, regenerates every three to five days. With age or injury — from radiation therapy, for example — that regeneration can slow or stop, leading to inflammation and conditions such as leaky gut syndrome.
Researchers at Cold Spring Harbor have found that eliminating damaged, aging cells from the intestine can restore its ability to regenerate. The approach uses CAR T cell therapy, a form of immunotherapy in which immune cells are engineered to recognize and destroy specific targets.
Amor Vegas, who is originally from Spain, said her lab focuses on aging and a process known as cellular senescence.
“Cells in your body, they accumulate a lot of damage,” she said. “Over time, they stop doing their normal job, and they instead become really pre-inflammatory. They cause a lot of damage in tissues.”
Senescent cells do not divide or die, but secrete signals that activate the immune system unnecessarily, leading to chronic inflammation. As people age, these cells accumulate, and have been linked to diseases such as diabetes, fibrosis and dementia.
Amor Vegas came to the lab in January 2022 after completing her medical training in at the Universidad Complutense de Madrid and earning a Ph.D. in cancer biology at Memorial Sloan Kettering Cancer Center. She now leads a group of eight scientists, including postdoctoral researchers, graduate students and technical staff, who engineer immune cells to target senescent cells. They have experimented by extracting immune cells from mice, modifying them in the lab to recognize senescent cells and then injecting them back into the animals.
The modified immune cells are known as chimeric antigen receptor T, or CAR T, cells. The team engineered them to target uPAR, a marker found on senescent cells. Amor Vegas said that only one injection was needed for the treatment to have lasting effects.
“[The CAR T cell] redirects the immune cells to recognize the senescent cells,” she said. “We take [the cells], we train them and then we put them back.”
To study the intestine, the team treated both young and old mice with the engineered cells. Treated animals showed reduced inflammation, fewer senescent cells and an increase in healthy stem cells in the intestinal lining. The intestine was better able to absorb nutrients and regenerate after injury.
“In both cases, we see really significant improvements,” Amor Vegas said. “They’re able to absorb nutrients better. They have much less inflammation. When irritated or injured, their epithelial lining is able to regenerate and heal much faster.”
The research has particular implications for cancer patients who undergo pelvic or abdominal radiation therapy, which often damages the intestinal lining. The team simulated radiation treatment in mice and found that those receiving CAR T cell therapy recovered much better than those that were not treated. A single treatment improved gut health for at least a year.
The work took roughly three years to complete and an additional year to prepare for publication. Amor Vegas said the team was careful not to overinterpret early results.
“We feel really excited, but we tried to take it slowly,” she said. “We try to not get overly excited over just one piece of data.”
According to a news release, the researchers also found evidence that the approach promotes regeneration in human intestinal and colorectal cells grown in laboratory settings. Exactly how the process works remains under investigation.
Beyond gut health, Amor Vegas said, the treatment has shown broader effects related to aging.
“We’ve seen a lot of effects on metabolism,” she said. “Now we’re seeing regeneration, and we have some data as well on cognitive functions.”
Despite the promise, Amor Vegas emphasized that the goal is not to affect the normal aging process.
“Aging is part of life, right?” she said. “We would give it to patients that have age-related diseases.”
Conditions such as fibrosis, diabetes and dementia, she explained, could be potential targets if the therapy advances to clinical trials. The next step, she said, would involve scaling up production of the engineered cells and securing funding to launch a startup company capable of supporting human trials.
Bruce Stillman, the laboratory’s president and CEO, said the research reflects the institution’s mission.
“People living with age-related diseases often endure symptoms for years, with few effective options to restore normal tissue function,” Stillman said in a statement. “Corina’s work, alongside her colleagues at Cold Spring Harbor Laboratory, is pioneering.”
He added that the research has the potential to “significantly improve quality of life,” calling it an example of the lab’s belief that “science makes life better.”
Amor Vegas said that responsible use of the science is essential. The long-term aim, she said, is to reduce the number of years people spend with chronic illness.
“We’ve all seen patients that maybe they’re spending even 10 years with terrible dementia,” she said. “I think that’s horrible. So really, that’s what we’re trying to avoid.”
