Ageing May Limit Success of CAR-T Cancer Therapy: Study

New Delhi: A new study published in Nature Cancer has found that aging significantly affects the efficacy of CAR-T cell therapy — a cutting-edge cancer immunotherapy — by impairing immune cell metabolism. The research highlights how a decline in mitochondrial function in older patients could compromise the therapy’s success, but also points to promising strategies for overcoming these age-related barriers.

CAR-T (chimeric antigen receptor T-cell) therapy involves genetically modifying a patient’s T cells to recognize and destroy cancer cells. It has shown remarkable success in treating certain types of blood cancers. However, researchers from a collaboration of top Swiss institutions, including the University of Lausanne (UNIL), Lausanne University Hospital (CHUV), Geneva University Hospitals (HUG), and the École Polytechnique Fédérale de Lausanne (EPFL), have now discovered that CAR-T cells from aged mice perform poorly compared to those from younger counterparts.

The study found that CAR-T cells in aged animals exhibited diminished mitochondrial function, reduced "stemness" (a measure of a cell’s ability to renew itself), and weakened antitumor activity. These impairments were traced to reduced levels of nicotinamide adenine dinucleotide (NAD), a key molecule involved in cellular energy production and mitochondrial health.

"CAR-T cells from older individuals are metabolically impaired and significantly less effective," said Dr. Helen Carrasco Hope, one of the lead authors. "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."

The researchers used NAD-boosting compounds currently under investigation for other health conditions, showing the potential for clinical translation. Their findings underscore the importance of accounting for age-related biological changes when designing and testing immunotherapies.

"This is a major step toward personalised and age-conscious immunotherapy," added Dr. Nicola Vannini, senior author of the study. "By correcting age-related metabolic defects, we could improve treatment outcomes for a significant portion of cancer patients — especially older adults, who represent the majority of cases."

The researchers are now calling for age to be a standard factor in preclinical and clinical evaluations of cell-based therapies. Their work emphasizes that biological ageing — not just chronological age — plays a crucial role in shaping how patients respond to advanced cancer treatments like CAR-T therapy.