Treatment with cord blood-derived chimeric antigen receptor (CAR) natural killer (NK)-cell therapy targeting CD19 resulted in clinical responses in a majority of patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) with no major toxicities based on a phase 1/2a trial published in Nature Communications.

Of the 11 patients participating in the study, 8 (73%) responded to the therapy and 7 of those achieved a complete response, meaning that they no longer showed evidence of disease at a median follow-up of 13.8 months.

Post-remission therapy was administered to 5 of the responding patients, and no patients experienced cytokine release syndrome or neurotoxicity. Responses to the CD19 CAR NK-cell therapy were evident within 1 month following infusion, and persistence of these cells was confirmed out to 1 year post-infusion.

“We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need,” said corresponding author Katy Rezvani, MD, PhD, professor of Stem Cell Transplantation and Cellular Therapy.

CAR NK cells are allogeneic, meaning that the cells are taken from a non-related healthy donor rather than the patient themselves. Therefore, CAR NK cells have the potential to be manufactured in advance and stored for immediate use. In contrast, current commercially available CAR T cells require the use of a patient’s own genetically modified T cells, created through a multi-week manufacturing process.

At The University of Texas MD Anderson Cancer Center, NK cells are isolated from donated umbilical cord blood and genetically engineered to express the desired CAR, which recognizes cancer-specific targets. The CAR NK cells also have IL-15, an immune signaling molecule designed to enhance the proliferation and survival of the cells. The CD19 CAR NK cells used in the study were designed to target B-cell malignancies.

The clinical trial included 11 patients who received a single dose of cord blood-derived CD19 CAR NK cells administered at 1 of 3 dose levels. Five patients diagnosed with CLL and 6 had NHL. All patients had been treated with a minimum of 3 and maximum of 11 lines of prior therapy. The first 9 patients treated received CD19 CAR NK cells that were partially matched according to the patient’s human leukocyte antigen (HLA) type, but the protocol allowed the final 2 patients to be treated with no HLA matching.

Adverse events (AEs) were related to the conditioning chemotherapy given before cell infusion within 1 to 2 weeks. No patient required admission to an intensive care unit for management of treatment AEs.

“Due to the nature of the therapy, we’ve actually been able to administer it in an outpatient setting,” Rezvani said. “We look forward to building upon these results in larger multi-center trials as we work with Takeda to make this therapy available more broadly.”

Reference
  1. CD19 CAR NK-cell therapy achieves 73% response rate in patients with leukemia and lymphoma [news release]. Published February 5, 2020. https://medicalxpress.com/news/2020-02-cd19-car-nk-cell-therapy-response.html. Accessed March 6, 2020.