Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors
Enli Liu, David Marín, Pinaki P. Banerjee, Homer A. Macapinlac, Philip A. Thompson, Rafet Başar, Lucila Nassif Kerbauy, Bethany Overman, Peter F. Thall, Mecit Kaplan, Vandana Nandivada, Indresh Kaur, Ana Karen Nunez Cortes, Kai Cao, May Daher, Chitra Hosing, Evan N. Cohen, Partow Kebriaei, Rohtesh S. Mehta, Sattva S. Neelapu, Yago Nieto, Michael Wang, William G. Wierda, Michael J. Keating, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Abstract
BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS: CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. RESULTS: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. CONCLUSIONS: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).