Clinical grade production of IL-15 stimulated NK cells for early infusion in adult AML patients undergoing haploidentical stem cell transplantation with post-transplant cyclophosphamide

Background: Allogeneic stem cell transplantation is the treatment of choice for acute myeloid leukemia (AML) patients. Unmanipulated haploidentical transplantation (Haplo-HSCT) is commonly used for those AML patients who need a timely transplant and do not have a suitable matched donor, but relapse rates are still high, and improvements are needed. Adoptive immunotherapy using natural killer cells (NK cells) could be a promising tool to improved Haplo-HSCT but, to date, no optimal infusion and manufacturing protocols have been developed. Study Design and Methods: In this study, we describe a quick and reproducible protocol for clinical-grade production of haploidentical donor NK cells using double immunomagnetic depletion and enrichment protocol and overnight IL-15 stimulation. Results: Thus, we have obtained 8 viable and functional NK cell products that have been safely infused to five AML patients undergoing unmanipulated Haplo-HSCT. Discussion: Our results demonstrate the safety and feasibility of manufactured NK IL15 cells obtained from an adult allogeneic donor in the setting of haploidentical transplantation for AML patients.