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

Transfusion. 2022 Feb;62(2):374-385. doi: 10.1111/trf.16790. Epub 2022 Jan 13.

Abstract

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.

Keywords: acute myeloid leukemia; adoptive immunotherapy; cell therapy; immunomagnetic cell isolation; natural killer (NK) cells; non-manipulated haploidentical allogeneic stem cell transplantation; post-transplant cyclophosphamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Graft vs Host Disease* / drug therapy
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Interleukin-15
  • Killer Cells, Natural
  • Leukemia, Myeloid, Acute* / drug therapy

Substances

  • Interleukin-15
  • Cyclophosphamide