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Chronic lymphocytic leukemia and non-Hodgkin's lymphoma: CD19 CAR NK-cell therapy achieves 73% response rate

According to results from a phase I/IIa trial at The University of Texas MD Anderson Cancer Center, 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 observed.

The trial results were published in the New England Journal of Medicine ( NEJM ). Of the 11 patients participating in the study, eight ( 73% ) responded to therapy and seven of those achieved a complete response, meaning they no longer showed evidence of disease at a median follow-up of 13.8 months.
Post-remission therapy was administered to five of the responding patients.

No patients experienced cytokine release syndrome or neurotoxicity.

Responses to the CD19 CAR NK cell therapy were evident within one month following infusion, and persistence of these cells was confirmed out to one year post-infusion.

CAR NK cells are allogeneic, meaning the cells are taken from a non-related healthy donor rather than the patient themselves. Thus, CAR NK cells have the potential to be manufactured in advance and stored for off-the-shelf immediate use.
In contrast, currently 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 MD Anderson, 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 are armored with IL-15, an immune signaling molecule that is designed to enhance proliferation and survival of the cells.
The CD19 CAR NK cells used in this study were designed to target B-cell malignancies.

On the clinical trial, 11 patients received a single dose of cord blood-derived CD19 CAR NK cells, administered at one of three dose levels.
Five patients had chronic lymphocytic leukemia and six had non-Hodgkin's lymphoma.
All patients were treated with a minimum of three and maximum of 11 lines of prior therapy. The first nine patients treated received CD19 CAR NK cells that were partially matched according to the individual's human leukocyte antigen ( HLA ) type, but the protocol allowed the final two patients to be treated with no HLA matching.

Side effects experienced by participants were primarily related to the conditioning chemotherapy given before cell infusion and were resolved within one to two weeks.
No patient required admission to an intensive care unit for management of treatment side effects. ( Xagena )

Source: University of Texas M. D. Anderson Cancer Center, 2020