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.
Background:
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.
Results:
- 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.
Conclusions:
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:
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
