HOUSTON, SEPTEMBER 25, 2026 – Researchers at The University of Texas MD Anderson Cancer Center have traced how off-the-shelf chimeric antigen receptor (CAR) T cells behave in patients, revealing how immune rejection and differences among CAR T cells influence their ability to multiply after infusion.
The findings, published today in Cancer Discovery , revealed that some patients' immune systems may reject donor-derived CAR T cells before they can fully expand and eliminate cancer. Researchers also identified specific CAR T cell populations that appear better equipped to multiply, persist, and destroy cancer cells.
"One of the biggest questions in the field has been why the same off-the-shelf CAR T cell therapy can lead to dramatically different results in different patients," said corresponding author Pavan Bachireddy, M.D. , assistant professor of Hematopoietic Biology and Malignancy and Scientific Director of the ECLIPSE platform. "By identifying both patient and CAR T cell characteristics that influence treatment response, we've uncovered insights that could help us develop more effective therapies for the future."
What is CAR T cell therapy?
CAR T cell therapy works by engineering and expanding T cells to better recognize and destroy cancer cells. Currently approved CAR T cell therapies are made from a patient's own cells, which involves a complex manufacturing process that can take weeks.
Off-the-shelf CAR T cell therapies are manufactured from healthy donor cells and can be available immediately when needed, offering the potential to reduce treatment delays and expand patient access. To date, researchers have not fully understood why donor-derived CAR T cells expand and remain active in some patients but fail to do so in others. Understanding those differences is critical because CAR T cell expansion after infusion is strongly linked to treatment success.
Why do some patients benefit from off-the-shelf CAR T cell therapy while others do not?
This study focused on patients with relapsed or refractory large B-cell lymphoma who received cemacabtagene ansegedleucel (cema-cel), an investigational off-the shelf CAR T cell therapy. Using advanced molecular and immune analyses, researchers tracked the behavior of CAR T cells after infusion and evaluated how patients' immune systems responded to them.
The study found that some patients had pre-existing immune cells capable of recognizing and attacking the donor-derived CAR T cells, essentially rejecting the treatment before it could work. Patients who experienced poor CAR T cell expansion had significantly higher levels of these immune responses. In contrast, patients whose CAR T cells expanded successfully showed little evidence of immune rejection.
Moreover, in these patients with successful CAR T expansion, researchers also discovered that CAR T cell "fitness" was critical. Across multiple donor-derived CAR T cell products and disease settings, certain CAR T cell populations consistently demonstrated a greater ability to multiply and persist. These data suggest that this biological principle of "fitness" may apply broadly across different off-the-shelf CAR T cell therapies.
How could these findings improve future CAR T cell therapies?
In this study, researchers established a framework for improving future allogeneic CAR T cell therapies, which includes identifying patients who are more likely to reject donor-derived CAR T cells before treatment begins. This allows for more personalized treatment strategies and interventions designed to minimize immune rejection. The study also points to opportunities for manufacturers to further optimize donor selection and production methods to generate CAR T cell products enriched with highly fit, expansion-capable immune cells.
