CAR T Cells Show Promise in Treating Aging-Related Diseases
Recent studies led by Memorial Sloan Kettering Cancer Center (MSK) and Cold Spring Harbor Laboratory reveal a groundbreaking application of chimeric antigen receptor (CAR) T cells in treating diseases associated with aging. While CAR T cell therapy has revolutionized the treatment of blood cancers, emerging evidence suggests its potential efficacy against other conditions, including autoimmune disorders and now, diseases related to aging.
The research, published in Nature Aging, demonstrates that CAR T cells engineered to target senescent cells - cells that halt division due to age or damage - hold significant therapeutic promise. In laboratory experiments, infusion of these engineered immune cells led to improved metabolic function in older mice and mice prematurely aged by a high-fat diet. Remarkably, even young, healthy mice administered a single dose of CAR T cells showed prevention of metabolic decline later in life.
Dr. Scott Lowe, senior study author and Chair of MSK's Cancer Biology and Genetics Program, underscores the broader implications of this research beyond cancer treatment. "When you hear 'CAR T cell therapy,' you think 'cancer' - but what we're learning is that this approach of engineering immune cells to target disease has much broader possibilities," he says.
The study findings revealed promising outcomes in mice subjected to metabolic stress induced by a high-fat diet. Following CAR T cell infusion, these mice exhibited lower body weight, improved fasting blood glucose levels, and enhanced glucose and insulin tolerance, despite continued high-fat diet intake. Notably, older mice experiencing decreased metabolic function due to natural aging also demonstrated significant improvement post-treatment.
Moreover, the therapeutic intervention did not induce any significant side effects, suggesting its safety and potential for clinical translation. While further research is warranted to explore the therapy's longevity benefits, Dr. Lowe emphasizes the significance of improving "healthspan" - the duration of healthy, disease-free life.
The study was co-led by graduate student Inés Fernández-Maestre from MSK and Dr. Corina Amor Vegas from Cold Spring Harbor Laboratory, both of whom played pivotal roles in advancing this research.
The therapeutic strategy targets senescent cells, characterized by their accumulation with age and contribution to chronic inflammation. CAR T cells designed to recognize and eliminate these cells offer a promising alternative to traditional small-molecule drugs. Dr. Lowe highlights the advantage of CAR T cell therapy's durability and potential for long-term efficacy.
Despite distinct challenges compared to cancer treatment, such as ensuring safety and addressing diseases with less lethal outcomes, CAR T cell therapy holds immense potential for revolutionizing the management of aging-related diseases. Dr. Michel Sadelain, a pioneer in CAR T cell therapy, underscores ongoing efforts to refine cellular therapies and expand their applicability across various disease contexts.
The research findings mark a significant milestone in the quest to harness the power of CAR T cells for combating age-related diseases, offering hope for a healthier and more vibrant aging population.