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Can T Cells From Lymphatic Fluid Benefit CAR T-Cell Therapy?

Published on October 7, 2020 in Cornerstone Blog · Last updated 4 months 3 weeks ago


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Researchers used lymphatic fluid to make CAR T cells.

The findings:

Researchers at Children’s Hospital of Philadelphia found that lymphatic fluid collected from the thoracic duct of children was rich in naïve T cells, which are crucial to making chimeric antigen receptor (CAR) T cells. They also found that CAR T cells generated from the lymphatic fluid appeared to be superior to those generated from the blood because they demonstrated higher cytotoxicity and were able to be given in lower doses.

Why it matters:

CAR T-cell therapy is a cellular therapy approved by the U.S. Food and Drug Administration to treat certain blood cancers. Scientists use T cells from a patient’s blood and modify them in the lab so that they attack the cancer.

Approximately 11% to 25% of patients who are eligible for CAR T-cell therapy are unable to undergo the therapy because the T cells collected are unable to expand. The T cells tend to be older and do not work as well in manufacturing CAR T cells. In previous studies, conducted in adult patients with HIV, researchers looked at T cells taken from the lymphatic system, rather than from the blood, and found that the T cells in the lymphatic system are younger, healthier, and more naïve. This study looked at whether similar T cells would be found in children’s lymphatic system.

Who conducted the study:

Jessica B. Foster, MD, attending physician in the Division of Oncology at CHOP, and instructor of Pediatrics at the University of Pennsylvania Perelman School of Medicine, was the first author of the study. Other collaborators include Yoav Dori, MD, PhD, a pediatric cardiologist and director of the Jill and Mark Fishman Center for Lymphatic Disorders at CHOP, and associate professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine; Stephan A. Grupp, MD, PhD, section chief of the Cellular Therapy and Transplant Section, director of the Cancer Immunotherapy Program, and medical director of the Cell and Gene Therapy Laboratory at CHOP, and Novotny Professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine; and David M. Barrett, MD, PhD, pediatric oncologist in the Cancer Center at CHOP and assistant professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine.

How they did it:

The study team evaluated lymphatic fluid collected from 25 pediatric patients who were undergoing thoracic duct cannulation for other indications. They compared the composition of the T cells obtained from the lymphatic fluid with the T cells obtained from the blood of the same patients. They also evaluated whether the CAR T cells generated from the lymphatic fluid had similar efficacy to those generated from the blood by working with an animal model of B-cell acute lymphoblastic leukemia.

Quick thoughts:

“These findings show us that there is a pool of T cells in patients that are ideal for making CAR T cells,” Dr. Foster said. “This is exciting because we have many patients who want to undergo CAR T cell therapy, but they are unable to do so because their T cells just won’t expand enough to produce CAR T cells. This opens up a completely different avenue to get T cells from those patients.”

What’s next:

The next step is for the Immunotherapy Program to develop clinical trial protocols to determine whether this procedure can be conducted in patients, Dr. Foster said.

Where the study was published:

The findings appeared in Cytotherapy.

Where to learn more:

Learn more about CAR T-cell therapy.