medwireNews: A first-in-man phase I trial highlights the potential of an immunotherapeutic approach using preactivated natural killer (NK) cells in patients with relapsed or refractory acute myeloid leukaemia (AML).
These cytokine-induced memory-like NK cells develop from primary human NK cells primed with interleukin (IL)-12, IL-15 and IL-18, explain the researchers who found that the memory-like NK cells were significantly more cytotoxic against leukaemia cell lines and primary AML blast cells relative to control NK cells.
And in AML patients not eligible for haematopoietic cell transplantation, treatment with memory-like NK cells led to a complete remission with or without complete blood count recovery in four of nine evaluable patients, while one patient achieved a morphological leukaemia-free state. This gave an overall response rate of 55%, which “is promising since these are patients with very poor prognoses and very few options”, lead author Todd Fehniger (Washington University School of Medicine, St Louis, Missouri, USA) told the press.
In all, 13 patients received an infusion of memory-like NK cells, generated from donor NK cells, at one of three doses (0.5 × 106/kg, 1.0 × 106/kg or all NK cells generated, capped at 10.0 × 106/kg) after a preconditioning regimen of fludarabine plus cyclophosphamide. But four participants were not evaluable due to infection-related death in three cases and insufficient donor cell availability as a result of technical failure in one.
“Because our sample size was limited, this finding is hypothesis-generating and will need to be studied in more patients treated with IL-12, IL-15, and IL-18–preactivated NK cells”, the researchers write.
Nonetheless, Fehniger told the media that they are “cautiously optimistic about these results.”
He continued: “There’s so much variability in how an individual patient responds to treatment, but this particular immunotherapy does seem to be inducing remissions in patients for whom other therapies, including similar investigational immune therapies, have a small chance of working.”
As reported in Science Translational Medicine, the clinical trial in AML patients was preceded by experiments in mice in which leukaemia was induced by engrafting K562 leukaemia cells. The tumour burden was reduced in mice that received human memory-like NK cells relative to those injected with control NK cells, and overall survival was also prolonged in the experimental versus control group.
By Shreeya Nanda
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