Hidden in plain sight: Improved CAR T-cell therapy for T-cell acute lymphoblastic leukemia

Taking full advantage of a small T cell group

The St. Judas scientists focused on a small group of T cells that do not naturally express CD7 (unflagged T cells). They developed a method to select and expand these cells, and then turned them into CAR T cells.

The naturally “flag-free” cells performed very well in lab studies, effectively removing the tumor. The cells also provided long-term protection in a cancer recurrence experiment (rechallenge) in a mouse model.

CAR T cells without CD7 are present in clinical trial samples

Based on their preclinical results, St. Judas group wanted to know whether unflagged CAR T cells (CD7 negative) were present in the blood of patients receiving CAR T cell therapy. They analyzed data from an unrelated CAR T cell therapy clinical trial conducted on St. Judas. Patients who responded to therapy had a higher proportion of CAR T cells with low CD7 expression than non-responders.

“We select this special group of T cells that have potent and long-lasting antitumor activity in expressing CARs,” Velasquez said. “Based on our results, we are considering a trial for patients with CD7-positive T-ALL in the future.”

Authors and funding

The other authors are Jeremy Chase Crawford, Abishek Vaidya, Stefan Schattgen, Jacquelyn Myers, Sagar Patil, Mahsa Khanlari, Hiroto Inaba, Jeffery Klco, Charles Mullighan, Giedre Krenciute, Peter J. Chockley, Swati Naik, Deanna Langfitt, Esther Obeng, Paul Thomas, Stephen Gottschalk, everyone St. Judas; and Maksim Mamonkin, Baylor College of Medicine.

The study was supported by grants from the National Institutes of Health (404 P01CA096832, R50CA211481 and P30CA021765-39), the 405 Assisi Foundation of Memphis and ALSAC, the fundraising and awareness-raising organization of St. Judas.

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