Summary:
Immunotherapy has rapidly advanced the field of medicine and has saved countless lives. The approach is much different than using an external chemical, such as in the case of chemotherapy. Immunotherapy leverages the body’s own immune system to recognize and attack foreign pathogens, specifically cancer. While there are many versions of immunotherapy, one rising star among them is known as Chimeric Antigen Receptor (CAR) T cell therapy. This therapy (usually) takes a patient’s own cells in the blood to generate engineered immune or T cells to fight the tumor. T cells are a critical immune cell population responsible for killing or lysing infected cells. In the case of CAR T cell therapy, the T cells from the patient are engineered to recognize receptors on the tumor. The CAR T-cells are then triggered to release different proteins and lyse the tumor cells. This type of therapy has revolutionized the way we treat patients with hematopoietic malignancies or blood cancers. CAR T-cell therapy gained Food and Drug Administration (FDA) approval in 2017 and is currently in clinical trials for many different lymphomas. Although the therapy started out treating blood cancers, researchers are broadening the scope of CAR T cell application to autoimmune disorders and recently in age-related diseases.
A collaboration between Memorial Sloan Kettering Cancer Center (MSK) and Cold Spring Harbor Laboratory has investigated CAR T-cell therapy in diseases relating to age. The therapy is employed to specifically target senescent cells – cells that cannot divide due to age or damage.
The recent article published in Nature Aging from the lab of Dr. Scott Lowe found that CAR T-cells engineered to target senescent cells improves metabolic function in mice. Lowe and collaborators fed young mice a high-fat diet for an extended period of time (2-months), which caused metabolic stress within the cells. These mice were then treated with CAR T-cell therapy. The results indicated that the treated mice lost weight, had improved blood glucose levels, and improved sensitivity to glucose and insulin. These results occurred even with the mice still on the high-fat diet. Interestingly, they had much lower senescent cell levels throughout the body. Similar results were found with older mouse due to natural aging. In addition, CAR T-cell treated aged mice were recorded to exercise longer than non-treated aged mice. These results demonstrate significant promise for therapeutic strategies against age-related disease, such as chronic obstructive pulmonary disease (COPD), and provide a deeper understanding into the process of aging itself.
Overall, Lowe and his team found that senescent-targeted CAR T-cell therapy improves metabolic function in aged mice and improves and maintains healthy metabolic function in high-fat diet young mice. These fundamental findings significantly enhance our understanding of cell biology and how to better target diseases associated with aging. Additionally, it provides alternative therapeutic strategies for improved quality of life in patients. Consequently, this new therapeutic strategy advances the field of aging and has the potential to significantly prolong patient survival.
Article, Nature Aging, Scott Lowe, MSK, Cold Spring Harbor Laboratory
