title: Activated natural killer cells from patients with acute myeloid leukemia are cytotoxic against autologous leukemic blasts in NOD/SCID mice.
abstract: Natural killer (NK) cells are implicated in the surveillance of hematological malignancies. They participate in the immune response against residual acute myeloid leukemia (AML) after hematopoietic stem cell transplantation with partial HLA class I disparity. However, the role of NK cells in autologous leukemia-specific immunity remains poorly understood. We studied the function of NK cells in AML patients at diagnosis. Following isolation, CD56+CD3- cells exhibited a high proliferative potential in vitro in response to interleukin (IL)-2. The polyclonal population of activated AML-NK cells expressed normal levels of the activating receptor NKG2D and the major natural cytotoxicity receptor NKp46. AML-NK cells were highly effective with respect to interferon-gamma production, cytotoxicity against HLA class I-deficient K562 erythroleukemia cells in vitro and retardation of tumor growth in vivo in K562-bearing NOD/SCID mice. Importantly, when AML blasts were injected into NOD/SCID mice, a single dose of adoptively transferred autologous AML-NK cells significantly reduced the AML load by 8-77%. Recognition of AML blasts may be related to the observed upregulation of ligands for NKG2D and natural cytotoxicity receptors in vivo. We conclude that AML patient-derived NK cells are fully functional, in support of exploring the benefit of AML immunotherapy with IL-2-stimulated autologous NK cells.
authors.affiliation: Department of Research, University Hospital Basel, Basel, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Siegler
authors.forename: C P
authors.initials: CP
authors.lastname: Kalberer
authors.forename: P
authors.initials: P
authors.lastname: Nowbakht
authors.forename: S
authors.initials: S
authors.lastname: Sendelov
authors.forename: S
authors.initials: S
authors.lastname: Meyer-Monard
authors.forename: A
authors.initials: A
authors.lastname: Wodnar-Filipowicz
mesh_terms: D000208:Acute Disease; D000818:Animals; D001752:Blast Crisis / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000502:physiology* / Q000637:transplantation; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D015854:Up-Regulation