Discussion
’ leukemia blast status, leukemia blasts, toxicity, leukemia, AML, Acute myeloid leukemia, leukemia blast reduction
SIDE EFFECT, LEUKEMIA, DISEASE, ACUTE MYELOID LEUKEMIA, AML, HEMATOLOGIC MALIGNANCIES
Acute myeloid leukemia is one of the most lethal hematologic malignancies, for which many advanced therapies are used worldwide. Employing natural killer cells as the main arm of innate immunity can be effective as a complementary treatment. Allogeneic off-the-shelf cell therapy using natural killer cells can change the patients’ fate, and its developmental studies are essential for commercialization after safety, feasibility and efficacy study [In this project, we expanded PB-NK cells by stimulation with irradiated autologous feeder cells to produce expanded and functional PB-NK cells [This phase I study using allogeneic NK cells allowed us to draw some clinical insights for patients with relapsed/refractory AML. The original hypothesis for this trial was that, given the previous successful therapy of leukemia by NK cells from alloreactive haploidentical KIR ligand-mismatched cells, administration of MG4101 would be safe and display improved clinical benefit over other treatments [Organ function characterized by biochemical assays in patients’ serum. The serum levels of SGOT, SGPT, Cr, and ALP were in the normal range in all patients except one of those patients (P01) who died due to COVID-19; hence, she was not evaluated. Normal liver function showed that there is no side effect of conditioning regimen and cell infusion on normal homeostasis [These results agree with those of previous studies of individuals treated with adoptive allogenic NK cell therapy [Some groups are exploring allogenic NK cell expansion using platforms with and without feeder [For patients with AML that are not candidates for HSCT and are chemo-refractor, treatment options are limited. Because PB-NK cells mediate strong GVL, their transfer may be beneficial for patients with relapsed/refractory AML. We conducted a phase 1 trial that demonstrated that PB-NK cell delivery was safe and feasible. No DLT was observed in relapsed/refractory AML patients who received 10 infusions of PB-NK cells. Some cases that developed infusion-related toxicity were responsive to supportive care.We expected that the transfer of PB-NK cells would result in at least stable disease in relapsed/refractory AML due to leukemia blast reduction by transferred PB-NK cells. Thus, the patients’ leukemia blast status was monitored before and after therapy. After allogenic NK cell infusion, in some patients, no significant change in the percentage of leukemia blasts was detected. The most important goal of this project was the feasibility and safety assessment of NK cell production and infusion after conditioning regimen in patients with AML. Due to the CONSORT checklist, our study evaluates well in case of feasibility parameters.This trial was not designed to characterize PB-NK cells after administration. This limitation will be evaluated by a complete analysis of donor NK-cell persistence and blood cytokines on infused PB-NK cells in a planned phase II trial. Chimerism levels of NK cells at 7 or 14 days after administration have been correlated with CR after IL-2-activated haploidentical NK cells [In summary, this trial supports the safety and feasibility of expanded PB-NK cells for effective “off-the-shelf” immunotherapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy. This capability, together with the apparently minimal HLA-matching requirements between the donor and recipient of NK cells, may pave the way for a truly off-the-shelf product that could increase treatment accessibility for more patients. The most important limitation in this study was the small sample size, and it was about the aim of study in case of NK cell infusion safety and feasibility evaluation in dose escalation setting. Eventually, since 10 × 10