Using CAR T Cell Therapy To Reverse Aging

Advances in medicine have helped people to live longer and healthier lives, as demonstrated by the growth of the number of centenarians. However, this aging population brings with it a host of issues, as well as new measures and methods that scientists are exploring such as keeping the immune system effective as we age. 

Lymphocytes (a type of white blood cell) are an important part of the immune system that helps the body find and destroy potentially harmful pathogens. These T cells are unique in that different T cells are designed to seek and destroy specific pathogens. They are made within the bone marrow and move to the thymus gland to continue developing. Once mature, they travel to tissues and organs within the lymphatic system and circulate within the bloodstream. 

“T cells have the ability to develop memory and persist in your body for really long periods, which is very different from a chemical drug. With CAR T cells, you have the potential of getting this one treatment, and then that’s it. For chronic pathologies, that’s a huge advantage. Think about patients who need treatment multiple times per day versus you get an infusion, and then you’re good to go for multiple years,” explains Dr. Corina Amor Vegas. 

Scientists have been investigating using T cells to fight cancer, which has led to the development of a type of immunotherapy called chimeric antigen receptor (CAR) T-cell therapy, which has also been used in research for the treatment of diseases other than cancer such as viral infections and autoimmune diseases. This study focused on using T cells as a potential way to fight aging because the immune system is effective at eliminating damaged senescent cells in younger people. 

“Thus, we wondered whether in aging we could redirect and repower the T cells to eliminate the damaged cells that accumulate,” said Dr. Corina Amor Vegas, assistant professor at Cold Spring Harbor Laboratory (CSHL) and lead author of this study.

“Senescent cells are cells in our body that have accumulated a lot of damage and as a result, they have stopped doing their normal jobs and instead become very inflammatory. The accumulation of these cells in tissues is really deleterious because it creates a severe proinflammatory microenvironment that prevents the other cells in the tissue from working properly too.,” said Vegas.

In animal studies, the team found that they could use CAR T cell therapy to eliminate senescent cells in mice. The mice treated with CAR T cell therapy to remove senescent cells were observed to become healthier with lower body weight, improved metabolism, improved glucose tolerance, and increased physical activity, according to the researchers. 

“We were very excited to see that the CAR T cells were able to eliminate the senescent cells and drive these effects,” Dr. Amor Vegas said. “We were also really excited about the long-term durability of these effects.”

“Interestingly, in our work, we saw not only therapeutic effects when we treated aged animals but we also saw preventive effects,” she continued. “Thus, when we treated young animals — once, only in their youth — and we let them age, they aged better.”

“If we give it to aged mice, they rejuvenate. If we give it to young mice, they age slower. No other therapy right now can do this.”

“Nonetheless it’s a long road and there is still a lot more research that needs to be done to optimize the approach,” Vegas added.

“(Dr. Amor Vegas’) study discovers an innovative strategy that can be leveraged to not only address these questions but also to facilitate the elimination of senescent cells,” said Dr. Yi Zhang, director member of the Center for Discovery and Innovation (CDI), professor at Hackensack Meridian School of Medicine at Hackensack Meridian Health in New Jersey, and co-leader of the Cancer-Host-Interaction Program at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. 

“In addition, given the fact that CAR T-cell treatment has transformed (the) treatment of cancer in human patients, this study also provides a proof-of-concept that programming T cells with CARs specific to markers associated with senescent cells will find new applications to improving the health of aging humans,” said Zhang. “Many efforts have been made to develop small molecule drugs to clear senescent cells, namely senolytic therapies. However, these studies are limited by poorly defined molecular pathways that mediate senescence and its associated chronic inflammatory damage to normal tissues during aging. Future research is needed to address this issue. In addition, it is important to investigate how the study using a mouse system can be translated into a senolytic therapy in humans.”