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

Making the most of a small T cell group

The St. Jude scientists focused on a small group of T cells that naturally do not express CD7 (T cells without a flag). They generated a method to select and expand these cells, and then made them into CAR T cells.

The naturally ‘flag-free’ cells performed very well in laboratory studies, effectively clearing 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, the St. Jude group wanted to know if there were CAR T cells without a flag (CD7 negative) present in the blood of patients receiving CAR T cell therapy. They analyzed data from an unrelated CAR T-cell therapy clinical trial performed at St. Jude. Patients who responded to the therapy had a higher proportion of CAR T cells with low CD7 expression than non-responders.

“We’re selecting this special group of T cells that have potent and lasting antitumor activity when expressing CARs,” Velasquez said. “Based on our results, we’re 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, all of St. Jude; 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 organization of St. Jude.

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