2020 February 06; 382(6): 545–553 | Enli Liu, M.D., David Marin, M.D., Pinaki Banerjee, Ph.D., Homer A. Macapinlac, M.D., Philip Thompson, M.B., B.S., Rafet Basar, M.D., Lucila Nassif Kerbauy, M.D., Bethany Overman, B.S.N., Peter Thall, Ph.D., Mecit Kaplan, M.S., Vandana Nandivada, M.S., Indresh Kaur, Ph.D., Ana Nunez Cortes, M.D., Kai Cao, M.D., May Daher, M.D., Chitra Hosing, M.D., Evan N. Cohen, Ph.D., Partow Kebriaei, M.D., Rohtesh Mehta, M.D., Sattva Neelapu, M.D., Yago Nieto, M.D., Ph.D., Michael Wang, M.D., William Wierda, M.D., Ph.D., Michael Keating, M.D., Richard Champlin, M.D., Elizabeth J. Shpall, M.D., Katayoun Rezvani, M.D., Ph.D.
This study evaluates the safety and efficacy of CAR-modified natural killer (NK) cells in patients with relapsed or refractory CD19-positive cancers. The trial involved 11 patients who received HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood. The cells were transduced with a retroviral vector encoding the anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and infused at three doses after lymphodepleting chemotherapy. The results showed that CAR-NK cell infusion was well-tolerated, with no significant toxic effects such as cytokine release syndrome, neurotoxicity, or graft-versus-host disease. Eight out of 11 patients (73%) had a response, including seven with complete remission. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. The study suggests that CAR-NK cells may be a promising alternative to CAR T cells for treating CD19-positive cancers, offering a safer and more accessible treatment option.This study evaluates the safety and efficacy of CAR-modified natural killer (NK) cells in patients with relapsed or refractory CD19-positive cancers. The trial involved 11 patients who received HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood. The cells were transduced with a retroviral vector encoding the anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and infused at three doses after lymphodepleting chemotherapy. The results showed that CAR-NK cell infusion was well-tolerated, with no significant toxic effects such as cytokine release syndrome, neurotoxicity, or graft-versus-host disease. Eight out of 11 patients (73%) had a response, including seven with complete remission. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. The study suggests that CAR-NK cells may be a promising alternative to CAR T cells for treating CD19-positive cancers, offering a safer and more accessible treatment option.