Aging Impairs CAR-T Cell Function by Disrupting Cellular Metabolism, New Research Finds

As individuals grow older, their immune system's ability to fight diseases diminishes, complicating the effectiveness of advanced immunotherapies like CAR-T cell therapy. A recent study published in Nature Cancer by researchers from the University of Lausanne, Lausanne University Hospital, Geneva University Hospitals, and EPFL investigates how age-associated immune decline impacts cancer treatment outcomes. The research reveals that CAR-T cells derived from aged models exhibit compromised mitochondrial function, decreased 'stemness,' and lowered antitumor activity. A key factor identified is the reduction of nicotinamide adenine dinucleotide (NAD), a vital molecule for cellular energy production and mitochondrial health. Dr. Helen Carrasco Hope, the study's first author, noted that aged CAR-T cells are metabolically less efficient, leading to diminished therapeutic potential. Importantly, the team demonstrated that restoring NAD levels in these cells can rejuvenate their antitumor capabilities, which suggests a potential translational approach for enhancing CAR-T therapy in older patients. The study further highlights that NAD-boosting compounds, already under clinical investigation for other conditions, could be repurposed to improve immunotherapy outcomes in the aging population. Dr. Nicola Vannini, senior author, emphasized that correcting age-related metabolic defects could significantly improve personalized cancer treatments for a large segment of patients who are currently underserved by current therapies. Overall, this research underscores the importance of considering biological age in developing and evaluating immunotherapies, advocating for more age-conscious approaches to cancer treatment.