Treatment Potential of CAR-Transduced Natural Killer Cells in CLL
Posted: Tuesday, April 14, 2020
Patients with relapsed or refractory CD19-positive cancers (including chronic lymphocytic leukemia [CLL]) responded to treatment with chimeric antigen receptor natural killer (CAR-NK) cell therapy, without the development of major toxicities. Enli Liu, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues published their phase I and II trial findings in The New England Journal of Medicine.
“The capability [to produce more than 100 doses of CAR-NK cells from a single cord-blood unit] together with the apparently minimal HLA-matching requirements between the donor of CAR-NK cells and the patient may pave the way for a truly off-the-shelf product that could increase treatment accessibility for many more patients,” concluded the authors.
The phase I and II trial recruited 11 patients with relapsed or refractory CD19-positive cancers including non-Hodgkin lymphoma and CLL. Patients were administered a single dose of HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood. These natural killer cells were transduced with a retroviral vector expressing anti-CD19 CAR, interleukin-15, and inducible caspase 9. Cells were expanded ex vivo and administered to patients after they had undergone lymphodepleting chemotherapy.
Among the 11 treated patients, 8 showed a response, with 7 patients achieving complete remission (4 with lymphoma and 3 with CLL). One patient had remission of the Richter’s transformation component of the disease but continued to have persistent CLL. All of these responses occurred within the first 30 days after infusion of the CAR-NK cells. In addition, the infused cells expanded and were persistent within patients at low levels for at least 12 months.
Treatment with the CAR-NK cells did not appear to induce cytokine-release syndrome, neurotoxicity, or graft-versus-host disease. Inflammatory cytokine levels in patients, including interleukin-6, did not increase over baseline. At the time the data were accrued, there was no antibody induction against mismatched HLA alleles of the infused product.
Disclosure: For full disclosures of the study authors, visit www.nejm.org.