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How Do CAR T-Cells Fare After One Decade?

Published on February 3, 2022 in Cornerstone Blog · Last updated 4 months 3 weeks ago
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In two patients infused with CAR T-cell therapy, highly activated CD4+ cells became the dominant CAR T cell subtype over 10 years.

In two patients infused with CAR T-cell therapy, highly activated CD4+ cells became the dominant CAR T cell subtype over 10 years.

The findings:

One decade after receiving chimeric antigen receptor (CAR) T cell therapy for chronic lymphocytic leukemia (CLL), two patients remain in remission showing detectable levels of cancer-fighting cells, according to new research from our Center for Single Cell Biology (CSCB) and the Division of Oncology. The two patients were infused as part of the phase I trial for CAR T-cell immunotherapy, a personalized treatment pioneered by researchers at CHOP and the University of Pennsylvania. Now, our researchers show that these patients’ highly activated CD4+ cells have become the dominant CAR T cell subtype, making up over 99.6 percent of cells in one patient and 97.6 percent in the other.

Why it matters:

Until now, CAR T-cell therapy’s long-term effects have not been studied. However, the new findings provide researchers with greater insight into which CAR T cell characteristics are associated with a strong anti-cancer response in leukemia, according to CSCB researchers. This information will help develop more refined treatments for cancer and other potential diseases. The findings also demonstrate the power of single-cell technologies to inform the development of cancer immunotherapy.

Who conducted the study:

Kai Tan, PhD, the study’s co-senior author, and Gregory Chen, co-lead author and an MD/PhD student in the Tan Lab, conducted the study along with Shovik Bandyopadhyay, MD/PhD student, Changya Chen and Peng Gao, postdoctoral fellows, and collaborators at the University of Pennsylvania.

How they did it:

Using cutting-edge single cell analysis, the researchers showed that the long-persisting CD4+ CAR T cells exhibited cytotoxic characteristics and ongoing functional activation and proliferation — even a decade after the patients were first treated. Single cell profiling also led them to discover that the dominance of CD4+ cells occurred during the patients’ remission phase.

Quick thoughts:

“This was a highly collaborative study that would have not been possible without the contribution of the physicians, scientists, trainees, and patients involved in the study at CHOP and PENN,” Dr. Tan said.

What’s next:

“There is tremendous development in the field of single-cell technologies,” Dr. Tan said. “We are excited to see how such technologies can be harvested to improve CAR-T therapy and more broadly gene and cell therapies.”

Where the study was published:

The study appeared in Nature.

Where to learn more:

Learn more about this study in the CHOP news brief and Penn Medicine press release. Learn more about CHOP’s role in pioneering CAR T cell therapy for children and how it works here.