#United States #Gut Health #CAR T-Cell #Cold Spring Harbor

Rejuvenating Gut Health with CAR T-Cell Therapy

As we grow older, many individuals notice that certain foods seem to cause digestive discomfort. This phenomenon can often be traced back to a deterioration of the intestinal epithelium, the protective layer comprised of a single cell layer that lines the gut. This layer plays a vital role in digestion and overall health. Typically, our intestinal epithelium renews itself every three to five days. However, factors such as aging or radiation from cancer treatments can hinder its regeneration, leading to inflammation and conditions like leaky gut syndrome.

A breakthrough has emerged from researchers at Cold Spring Harbor Laboratory (CSHL), where scientists have developed a novel method for stimulating growth and healing in intestinal cells. This innovation leverages CAR T-cell therapy, an advanced form of immunotherapy, setting the stage for future clinical trials that could enhance gut health for patients facing age-related challenges.

The research initiative is spearheaded by CSHL Assistant Professor Corina Amor Vegas, who specializes in cellular senescence. As age progresses, our bodies accumulate cells that cease to replicate yet remain alive. These senescent cells have been associated with a variety of age-related ailments, including diabetes and dementia. Amor Vegas's team previously engineered specially designed immune cells termed anti-uPAR CAR T cells, which target and eliminate these senescent cells, significantly boosting metabolic health in mice.

Curiosity sparked a new exploration: Could this approach also revitalize the intestine? To investigate, Amor Vegas partnered with fellow CSHL Assistant Professor Semir Beyaz and graduate student Onur Eskiocak. The team administered CAR T cells directly into the intestines of both older and younger mice. The results were remarkable. Amor Vegas stated, "In both age groups, significant improvements were observed. The mice showed enhanced nutrient absorption and considerably reduced inflammation. Additionally, their epithelial layer demonstrated an impressive capacity for regeneration and faster healing when injured."

Leaky gut syndrome is notably prevalent among cancer patients undergoing radiation therapy targeting the pelvis or abdomen. To mimic this treatment, the research team applied radiation to the intestinal cells of the mice. Interestingly, those receiving CAR T cells exhibited a much better recovery from such radiation damage compared to their counterparts who did not receive the treatment. Remarkably, just one dose of CAR T-cell therapy maintained improved gut health in the mice for over a year.

Furthermore, the research pointed to compelling evidence that anti-uPAR CAR T cells also encourage regeneration in human intestinal and colorectal tissues. Eskiocak remarked that while the precise mechanisms remain to be elucidated, the outcomes are highly promising. Beyaz summed up the potential impact of their research: "This marks an important step in our long endeavor to enhance healing processes in older individuals."

Founded in 1890, Cold Spring Harbor Laboratory has been a pioneer in modern biomedical research and education, with a focus on cancer, neuroscience, and several other scientific fields. Its contributions to science include eight Nobel Prize winners, showcasing the institution's long-standing commitment to innovation and excellence in research. For more details, visit Cold Spring Harbor Laboratory.