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Ex Vivo Expanded Adaptive NK Cells Effectively Kill Primary Acute Lymphoblastic Leukemia Cells
Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
INSERM, Imagine Inst, U1163, Human Genet Infect Dis Lab, Paris, France.;Paris Descartes Univ, Imagine Inst, Paris, France..
Oslo Univ Hosp, Inst Canc Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway..
Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
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2017 (English)In: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 5, no 8, 654-665 p.Article in journal (Refereed) Published
Abstract [en]

Manipulation of human natural killer (NK) cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIR), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL). Culture of polyclonal NK cells together with feeder cells expressing HLA-E, the ligand for the activating NKG2C receptor, led to selective expansion of adaptive NK cells with enhanced allor-eactivity against HLA-mismatched targets. The ex vivo expanded adaptive NK cells gradually obtained a more differentiated phenotype and were specific and highly efficient killers of allogeneic pediatric T-and precursor B-cell acute lymphoblastic leukemia (ALL) blasts, previously shown to be refractory to killing by autologous NK cells and the NK-cell line NK92 currently in clinical testing. Selective expansion of NK cells that express one single inhibitory KIR for self-HLA class I would allow exploitation of the full potential of NK-cell alloreactivity in cancer immunotherapy. In summary, our data suggest that adaptive NK cells may hold utility for therapy of refractory ALL, either as a bridge to transplant or for patients that lack stem cell donors.

Place, publisher, year, edition, pages
2017. Vol. 5, no 8, 654-665 p.
National Category
Immunology in the medical area Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-333070DOI: 10.1158/2326-6066.CIR-16-0296ISI: 000406676500004PubMedID: 28637877OAI: oai:DiVA.org:uu-333070DiVA: diva2:1155721
Funder
Swedish Childhood Cancer FoundationSwedish Cancer SocietySwedish Research CouncilThe Wenner-Gren FoundationThe Karolinska Institutet's Research FoundationEU, Horizon 2020, 692180-STREAMH2020-TWINN-2015
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2017-11-09Bibliographically approved

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