Corina Amor Vegas, a fourth-year student in the Gerstner Sloan Kettering Graduate School of Biomedical Sciences (GSK), has been awarded the 2020 Chairman’s Prize. The competitive award is presented annually and was established by GSK’s Board of Trustees Chair Louis V. Gerstner, Jr., for whom the school is named.
This year’s Chairman’s Prize, in the amount of $2,000, recognizes Dr. Amor’s research, which she conducted in the laboratory of Scott Lowe, Chair of the Cancer Biology & Genetics Program at Memorial Sloan Kettering (MSK). His lab studies tumor-suppressor networks and how their disruption influences the development of cancer.
Below, Dr. Amor describes her winning thesis work in which she developed a new technique using immunotherapy to selectively eliminate non-dividing cells known as senescent cells. These cells promote inflammation and have been implicated in many age-related diseases, such as lung and liver fibrosis, atherosclerosis, and osteoarthritis.
Senolytic CAR T Cells Reverse Senescence-Associated Pathologies
Chimeric antigen receptor (CAR) T cell therapy is an approach that uses your own immune cells to fight cancer. Developed by MSK immunologist Michel Sadelain and colleagues, it has shown remarkable efficacy in treating people with certain types of blood cancers. However, the application of CAR T cell therapy beyond cancer has not been explored.
My research centers on whether CAR T cells can also be harnessed to eliminate senescent cells. Previous attempts to kill senescent cells have focused on the use of small molecules that were used to treat cancer. However, these compounds lack potency and produce significant side effects.
We developed a unique approach to selectively eliminate senescent cells. To achieve this, we identified uPAR as a protein that is broadly upregulated in senescent cells and engineered senolytic CAR T cells able to target it. Our results showed for the first time that these senolytic CAR T cells were able to target senescent cells and produce a therapeutic response in mouse models of both liver fibrosis and lung cancer.
Our paper, published in the July 2020 issue of Nature, opens up a completely new strategy to eliminate senescent cells. More research is needed to identify additional CAR targets and CAR construct designs and to shed light on optimal approaches. Senolytic CAR T cells may have broad therapeutic potential for cancer and the so-called “senescence-associated diseases.”