MD Anderson emerges with strong evidence for natural killer cell therapy, and Takeda looks like a winner
As far as biological branding goes, it’s hard to beat natural killer cells.
These immune responders earned their moniker in the ’70s for their apparent ability to kill viruses and some tumor cells quickly and without initial training. And in recent years, as scientists began re-engineering T cells to attack evasive tumors and creating the first CAR-T treatments, researchers started seriously exploring how to do the same with natural killers.
Now, MD Anderson has emerged with some of the first clinical proof this can work. A team led by Katayoun Rezvani attached CARs – chimeric antigen receptors – for CD19 to natural killer cells and injected them into 11 patients with either non-Hodgkin lymphoma or chronic lymphocytic leukemia. Seven of them had a complete response; their tumors vanished.
The news is a step forward in natural killer cell research and for cancer cell therapy as a field. It’s also a good sign for Takeda, who licensed the therapy for an undisclosed sum in November as part of a broad push to reignite an ailing R&D engine. Results from the Phase I/II study were published in the New England Journal of Medicine.
Much of the interest around natural killer cell therapy, or CAR-NK, stems from their potential as a form of “off-the-shelf CAR-T.” CAR-T treatments such as Kite Pharma’s Yescarta and Novartis’ Kymriah have disappointed commercially because they have to be done using a patient’s own cells, setting off a long and costly process that both limit the number of patients it can help and potential profit. You can’t use donor T cells now in part because it would likely trigger graft-versus-host disease, although there are ongoing efforts to get around that and make an allogenic CAR-T.
But foreign natural killer cells don’t cause graft-versus-host disease. So rather than drawing millions of a patient’s cells, treating them with a receptor over weeks or months and then reinjecting them into a patient, Rezvani could use donated umbilical cord blood. For 9 of the 11 patients, the team found a partial donor match and for the last 2, the cells were completely mismatched. None of the patients experienced GVHD.
“We have shown that we can manufacture hundreds of doses of CAR NK cells from a single unit of cord blood,” Rezvani said in December. “Ultimately, our plan is to freeze and store these CAR NK cells in a cell bank so that when a patient comes to the clinic, we can take those CAR NK cells immediately from the bank to treat the patients, making this a truly off-the-shelf-product.”
Rezvani’s team took isolated natural killers cells from the umbilical cord blood, genetically modified them to identify cancers that would otherwise evade the cells, “armored” the natural killers with IL-15 and finally injected them into 11 patients who had already been through a median of 4 lines of therapy. Most began to respond within 30 days. After 13.8 months, seven were still disease-free, although the researchers said the actual duration of response couldn’t be measured because patients went on other therapies after receiving the CAR-NK.
The other benefit of natural killer cells is that they appear to not cause the main toxicity that CAR-T can cause: cytokine release syndrome, a potentially deadly scenario in which the modified immune cells release billions of inflammation-causing molecules. This syndrome is thought to be caused by IL-6, and natural killers give off far less of that protein than T cells.
The therapy could reach patients soon, at least by the standards of early-stage cancer studies. Takeda R&D chief Andy Plump told Endpoints News in November they were looking to initiate a pivotal trial in 2021.