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ASH 2022: Dr. Neil Kay on Senescence in CAR-T Cells

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

The Bottom Line:

This research shows that senescence (biological aging) can occur in CAR-T cells, reducing their ability to kill cancer cells.

Who Performed the Research and Where Was it Presented:

Dr. Neil Kay from Mayo Clinic and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022. This was a collaboration with Dr. Saad Kenderian from Mayo Clinic.


CAR-T (Chimeric Antigen Receptor T-cell) therapy is an immunotherapy that genetically trains an individual’s immune system (specifically the T-cells, a type of white blood cell) to recognize and attack cancerous cells. CAR-T involves taking cells from the patient and altering them to add a chimeric antigen receptor specifically made for different types of cancer and then reinfusing them back into the same patient. CAR-T therapy is still considered experimental for chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL) since patients with CLL / SLL typically do not respond vigorously to CAR-T therapy.

In this interview, Dr. Brian Koffman interviewed Dr. Neil Kay, a Professor of Medicine and a hematologist at the Mayo Clinic. They discussed a study examining whether CAR-T cells are becoming senescent, meaning they are aging and are not functioning normally. Senescent cells release chemicals that can trigger inflammation, and senescent T cells are less capable of killing infected cells than healthy T cells.

Methods and Participants:

This was a preclinical study with CAR-T cells in a dish in a laboratory. The researchers developed a cell culture model for repeated CAR-T cell activation followed by rest to study the development of senescence and its impact on T cell functions.


  • In this study, T cells were modified with different chimeric antigen receptors and then were “activated,” meaning exposed to cancer cells at different time points.
  • The CAR-T cells began expressing senescence markers after one or two exposures to cancer cells.
  • The CAR-T cells that were activated at later time points (meaning they had more exposure to cancer cells) were less effective at reducing tumor burden in a mouse model.


This research shows that senescence can occur in CAR-T cells, reducing their effectiveness. As a result, scientists are looking for ways to help CAR-T cells avoid senescence and increase their effectiveness.

Links and Resources:

Watch the interview on the abstract here:

ASH 2022: Dr. Neil Kay on Improving CAR-T Therapy in Chronic Lymphocytic Leukemia (CLL)

You can read the actual ASH abstract here: Differential Susceptibility to Senescence in CART Cells Based on Co-Stimulatory Signaling

Take care of yourself first.

Ann Liu, PhD