Anti-CD19 CAR-NK Cells Effectively Treat CD-19+ Lymphoma Without Toxicity

A phase 1/2 trial evaluating the use of HLA-mismatched anti-CD19 CAR-NK cells in patients with CD19-positive non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL) has demonstrated the efficacy of using these cells to treat CD-19-positive cancers without the toxic effects of CAR-T therapy (N Engl J Med. 2020;382(6):545-553).

“Anti-CD19 [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. [NK] cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations,” wrote Enli Liu, MD, University of Texas MD Anderson Cancer Center, Houston, and colleagues.

Researchers transduced NK cells with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin 15, and inducible caspase 9 as a safety switch. These cells were then expanded ex vivo and given to the 11 participating patients in a single infusion at 1 of 3 doses (1×105, 1×106, or 1×107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy.

The maximum tolerated dose was not reached, and there was no development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease reported. Nor were there any increases in the levels of inflammatory cytokines, including interleukin-6, over baseline associated with the administration of CAR-NK cells.

Furthermore, trial findings showed that 8 (73%) of the 11 patients had a response; 7 (4 with lymphoma and 3 with CLL) of whom had complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses to the treatment were 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.

“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,” concluded Dr Liu et al.—Alexandra Graziano