In vivo CAR T cells to treat and prevent neurodegeneration

Over the past 150 years, human life expectancy has increased dramatically. In contrast, healthspan, the proportion of life spent in good health, has remained largely unchanged, while the incidence of incurable, chronic age-related diseases, such as dementias, has soared. In my laboratory we aim to understand the biology of aging. Specifically, our research focuses on understanding how the accumulation of a small number of dysfunctional senescent cells in tissues drives organismal decline. By harnessing immune-based strategies, we are pioneering cell therapies that selectively target these damaged cells to treat age-related diseases. Our ultimate goal is to extend and improve human healthspan.

Dr. Amor Vegas is an assistant professor at Cold Spring Harbor Laboratory (CSHL) and a Howard Hughes Medical Institute Freeman Hrabowski Scholar. She received an M.D. from Universidad Complutense de Madrid in Spain and a PhD from the Gerstner Sloan Kettering Graduate School at Memorial Sloan Kettering Cancer Center in NY. Following graduation she established her own research group at Cold Spring Harbor Laboratory as an Independent Fellow in January 2022 and She became an assistant professor in 2024. Her laboratory studies aging biology with a focus on cellular senescence and she has developed the first CAR T cells able to eliminate senescent cells. The long-term goal of their research is to elucidate the contribution of senescent cells to the aging process and to develop novel cell-based therapeutic strategies to treat age-related pathologies. The impact of her research has been recognized by the National Institute of Health (F99/K00 and NIH Director’s Early Independence Award awards), Forbes (30 under 30) or the Howard Hughes Medical Institute (Freeman Hrabowski Scholar).

Neurodegenerative conditions like Alzheimer’s disease (AD), affecting over 6.7 million Americans, currently lack effective treatment and prevention strategies. CAR T cells, a form of immunotherapy in which the body’s T cells are redirected to target specific cell populations, could represent a possible therapeutic strategy. Initially developed for hematological malignancies, CAR T cells are highly effective and can also provide long term effects after single administration. However, the lack of viable targets, the need to administer them intracranially and the high cost of manufacturing have hindered their potential application to neurodegeneration.

While aging is a key risk factor for neurodegeneration, little is understood about how aging of the whole-body impacts brain biology. In our initial studies we have found that removing damaged, aging cells from tissues outside the brain with anti-aging CAR T cells can improve cognition in animal models of aging and AD. In this proposal we aim to: 1) Understand the mechanism whereby the aged cells outside the central nervous system contribute to neurodegeneration and 2) Develop safer and more scalable forms of CAR T cells that are generated directly inside the body, bypassing the need for complex cell manufacturing. Our goal is to develop a new class of long-term, safe, effective and affordable CAR T cells for neurodegeneration.

“I think innovation comes from having the drive, courage and a bit of “recklessness” to test that “crazy” new idea, even when everyone says it will never work. Ninety-nine percent of the time it will fail; and that’s ok, you will still learn from it. But that one percent of success is all you need to truly make a difference”.