At the heart of this decline was a significant reduction in levels of nicotinamide adenine dinucleotide (NAD), a molecule essential for mitochondrial health and cellular energy production
A new study has found that ageing can significantly impair the effectiveness of CAR-T cell therapy, one of the most advanced cancer immunotherapies available today. The research reveals that age-related changes in the immune system and cellular metabolism can reduce the ability of engineered T cells to fight cancer, but also points to a promising way to reverse this effect.
Chimeric Antigen Receptor T-cell (CAR-T) therapy involves modifying a patient’s T cells to target and destroy cancer cells. While this approach has shown remarkable results in treating certain blood cancers, the new findings suggest its success could be compromised in older patients.
The study, led by scientists from the University of Lausanne (UNIL), the Lausanne University Hospital (CHUV), the Geneva University Hospitals (HUG), and the Ecole Polytechnique Fédérale de Lausanne (EPFL), examined the functionality of CAR-T cells in aged mice. They found that CAR-T cells from older animals exhibited weaker mitochondrial function, diminished “stemness,” and reduced antitumour activity compared to those from younger subjects.
At the heart of this decline was a significant reduction in levels of nicotinamide adenine dinucleotide (NAD), a molecule essential for mitochondrial health and cellular energy production. “CAR-T cells from older individuals are metabolically impaired and significantly less effective,” said Dr. Helen Carrasco Hope, one of the study’s lead researchers. “What’s exciting is that we were able to rejuvenate these aged cells by restoring their NAD levels—reviving their antitumour function in preclinical models.”
Hope emphasized that the study adds to the growing understanding that ageing fundamentally reshapes immune cell function and metabolism. “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,” she said.
The research, published in the journal Nature Cancer, used NAD-boosting compounds currently under clinical investigation for other conditions. This makes the approach potentially applicable in human patients, offering a pathway to improve immunotherapy outcomes for older adults.
Senior author Dr. Nicola Vannini called the findings a “major step toward personalised and age-conscious immunotherapy.” He said that by addressing age-related metabolic defects, researchers could significantly improve CAR-T therapy outcomes for a larger segment of the cancer patient population.
“This study reinforces the concept that age is not just a chronological factor but a biological one that can shape how patients respond to therapy,” Vannini added.
Given the promising results, the researchers are urging that age be systematically factored into the development and evaluation of cell-based cancer therapies going forward.
The findings could ultimately help tailor immunotherapy strategies more effectively for older cancer patients, improving both access and outcomes in a group that often sees reduced benefit from cutting-edge treatments.
