Cancer treatments that depend on using immune cells have difficulties as people age because their immune systems become less effective. Researchers from the University of Lausanne (UNIL), Lausanne University Hospital (CHUV), Geneva University Hospitals (HUG), and Ecole Polytechnique Fédérale de Lausanne (EPFL) demonstrate in a recent study published in Nature Cancer that this age-related immune decline has a quantifiable effect on CAR-T cell therapy, one of the most cutting-edge types of cancer immunotherapy.
By teaching a patient’s T cells to identify and eliminate cancer cells, CAR-T treatment functions. However, the study discovered that CAR-T cells from elderly mice had decreased anticancer activity, poor mitochondrial function, and decreased “stemness.” Nicotinamide adenine dinucleotide (NAD), a chemical necessary for mitochondrial metabolism and cellular energy, is the culprit.
“CAR-T cells from older individuals are metabolically impaired and significantly less effective,” stated first author Dr. Helen Carrasco Hope. “What’s exciting is that we were able to rejuvenate these aged cells by restoring their NAD levels—reviving their antitumor function in preclinical models.”
“Our findings strengthen the growing recognition that aging fundamentally reshapes immune cell function and metabolism,” she attached. “They highlight the urgent need to model age more accurately in preclinical studies, so that therapies are developed with the real-world cancer population in mind—where most patients are older adults.”
The scientists showed that this strategy is transferable and maybe useful in people by using NAD-boosting drugs that are presently being studied clinically for various illnesses. “This is a major step toward personalized and age-conscious immunotherapy,” stated senior author Dr. Nicola Vannini. “By correcting age-related metabolic defects, we could improve outcomes for a large segment of cancer patients.”
The study contributes to a growing body of research that demonstrates that age is a biological element that can influence therapeutic response rather than just a calendar number. The authors urge that while developing and assessing cell-based immunotherapies, age be taken into account methodically.
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