Patients with certain types of relapsed/refractory leukemia or lymphoma showed a favorable response when treated with natural killer (NK) cells modified to express an anti-CD19 receptor, according to a recent study from the University of Texas MD Anderson Cancer Center in Houston.
In the study, 11 patients with CD19-positive chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma received the modified cells, known as chimeric antigen receptor-NK (CAR-NK) cells. Seven of the patients experienced complete remission, while in 1 other patient, treatment reduced the aggressiveness of their disease. The responses occurred within 30 days, and treatment was well tolerated. Administration of CAR-NK cells did not lead to cytokine release syndrome, an inflammatory response commonly seen after CAR-T cell therapy. The results were published in the New England Journal of Medicine.1
“I’m super excited about our data, and what we’ve seen in the patients, but I’m cognizant of the fact that this was a handful of patients,” said Katy Rezvani, MD, PhD, the study’s senior author. “We are making great strides, but we also have to be cautious in terms of what conclusions we can draw.”
Adoptive cell therapy using CAR-T cells has shown promise against CD19-positive cancers, but it’s hindered by several important drawbacks. For one thing, it requires isolating and modifying the patient’s own cells, which eats up valuable time. Because the patient will have already endured multiple rounds of therapy, it may not be possible to generate useful doses of CAR-T cells from the patient’s depleted supply. CAR-T cells also inflict some unpleasant side effects, including cytokine release syndrome (CRS), an inflammatory response that causes fatigue, body aches, and fever.
Some researchers are turning to NK cells as an alternative. The aptly named “natural killer” cells have the innate ability to hunt down and kill cancer cells, which makes them an enticing tool for potential therapies. Unfortunately, they don’t do well against some leukemias without a little help. Professor Dario Campana, MD, PhD, of the National University of Singapore was among the first to express CARs in NK cells.2 “We found at that time that acute lymphocytic leukemias were resistant to NK cells,” recalled Dr Campana, who was not involved in the current trial. “When you add the CAR, then the killing is tremendous. The CAR overrides any inhibitor signals that the NK cells have.”
In the current phase 1/2 trial, Dr Rezvani and her team created CAR-NK cells from banked cord blood cells. Because they lack the T-cell receptors that cause graft-vs-host disease, in which the transplanted cells attack the host’s own body, NK cells can come from an unrelated donor and don’t have to be human leukocyte antigen-matched. This means CAR-NK cells could one day be manufactured as an off-the-shelf product, rather than created specifically for each patient.
For this trial, each patient received CAR-NK cells developed from a separate cord blood donor, but Dr Rezvani said that, in theory, 1 donor could provide CAR-NK cells to multiple patients.
None of the 11 patients developed the CRS or neurotoxicity that have been observed in patients administered CAR-T cells, and they the researchers never reached the maximum tolerated dose. No increase in inflammatory cytokine levels was observed.