CAR-NK Cells Make Their Debut in Hematologic Cancers – Cancer Therapy Advisor

Patients with certaintypes of relapsed/refractory leukemia or lymphoma showed a favorable responsewhen treated with natural killer (NK) cells modified to express an anti-CD19receptor, according to a recent study from the University of Texas MD Anderson CancerCenter in Houston.

In the study, 11 patientswith CD19-positive chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphomareceived the modified cells, known as chimeric antigen receptor-NK (CAR-NK)cells. Seven of the patients experienced complete remission, while in 1 otherpatient, treatment reduced the aggressiveness of their disease. The responsesoccurred within 30 days, and treatment was well tolerated. Administration ofCAR-NK cells did not lead to cytokine release syndrome, an inflammatoryresponse commonly seen after CAR-T cell therapy. The results were published inthe New England Journal of Medicine.1

Im super excited aboutour data, and what weve seen in the patients, but Im cognizant of the factthat this was a handful of patients, said Katy Rezvani, MD, PhD, the studyssenior author. We are making great strides, but we also have to be cautious interms of what conclusions we can draw.

Adoptive cell therapyusing CAR-T cells has shown promise against CD19-positive cancers, but itshindered by several important drawbacks. For one thing, it requires isolatingand modifying the patients own cells, which eats up valuable time. Because thepatient will have already endured multiple rounds of therapy, it may not bepossible to generate useful doses of CAR-T cells from the patients depletedsupply. CAR-T cells also inflict some unpleasant side effects, includingcytokine release syndrome (CRS), an inflammatory response that causes fatigue,body aches, and fever.

Some researchers areturning to NK cells as an alternative. The aptly named natural killer cellshave the innate ability to hunt down and kill cancer cells, which makes them anenticing tool for potential therapies. Unfortunately, they dont do wellagainst some leukemias without a little help. Professor Dario Campana, MD, PhD,of the National University of Singapore was among the first to express CARs inNK cells.2 We found at that time that acute lymphocytic leukemiaswere resistant to NK cells, recalled Dr Campana, who was not involved in thecurrent trial. When you add the CAR, then the killing is tremendous. The CARoverrides any inhibitor signals that the NK cells have.

In the current phase 1/2trial, Dr Rezvani and her team created CAR-NK cells from banked cord bloodcells. Because they lack the T-cell receptors that cause graft-vs-host disease,in which the transplanted cells attack the hosts own body, NK cells can comefrom an unrelated donor and dont have to be human leukocyte antigen-matched.This means CAR-NK cells could one day be manufactured as an off-the-shelfproduct, rather than created specifically for each patient.

For this trial, eachpatient received CAR-NK cells developed from a separate cord blood donor, butDr Rezvani said that, in theory, 1 donor could provide CAR-NK cells to multiplepatients.

None of the 11 patientsdeveloped the CRS or neurotoxicity that have been observed in patientsadministered CAR-T cells, and they the researchers never reached the maximumtolerated dose. No increase in inflammatory cytokine levels was observed.

Read more:
CAR-NK Cells Make Their Debut in Hematologic Cancers - Cancer Therapy Advisor