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Adaptive single-KIR...
Adaptive single-KIR(+)NKG2C(+) NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
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- Haroun-Izquierdo, Alvaro (author)
- Karolinska Institutet
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- Vincenti, Marianna (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Netskar, Herman (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- van Ooijen, Hanna (author)
- KTH,Science for Life Laboratory, SciLifeLab,Tillämpad fysik
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- Zhang, Bin (author)
- Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
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- Bendzick, Laura (author)
- Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
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- Kanaya, Minoru (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Momayyezi, Pouria (author)
- Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden.
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- Li, Shuo (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Wiiger, Merete Thune (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Hoel, Hanna Julie (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Krokeide, Silje Zandstra (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Kremer, Veronika (author)
- Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden.
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- Tjonnfjord, Geir (author)
- Univ Oslo, Oslo Univ Hosp, Inst Clin Med, Dept Hematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr B cell malignancies, Oslo, Norway.
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- Berggren, Stephanie (author)
- Karolinska Univ Hosp, Karolinska Ctr, Cell Therapy Clin Res Ctr, Vecura, Stockholm, Sweden.
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- Wikström, Kristina (author)
- Karolinska Univ Hosp, Karolinska Ctr, Cell Therapy Clin Res Ctr, Vecura, Stockholm, Sweden.
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- Blomberg, Pontus (author)
- Karolinska Univ Hosp, Karolinska Ctr, Cell Therapy Clin Res Ctr, Vecura, Stockholm, Sweden.
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- Alici, Evren (author)
- Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Stockholm, Sweden.
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- Felices, Martin (author)
- Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
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- Önfelt, Björn (author)
- KTH,Tillämpad fysik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Microbiol Tumour & Cell Biol, Stockholm, Sweden.
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- Höglund, Petter (author)
- Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden.
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- Valamehr, Bahram (author)
- Fate Therapeut Inc, La Jolla, CA USA.
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- Ljunggren, Hans-Gustaf (author)
- Karolinska Institutet
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- Björklund, Andreas (author)
- Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden.
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- Hammer, Quirin (author)
- Karolinska Institutet
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- Kveberg, Lise (author)
- Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
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- Cichocki, Frank (author)
- Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
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- Miller, Jeffrey S. (author)
- Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
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- Malmberg, Karl-Johan (author)
- Karolinska Institutet
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- Sohlberg, Ebba (author)
- Karolinska Institutet
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Karolinska Institutet Univ Oslo, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway (creator_code:org_t)
- 2022-11-01
- 2022
- English.
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In: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:11, s. e005577-
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- BackgroundNatural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)(+)NKG2C(+) adaptive NK cells to maximize missing-self reactivity.MethodsWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ResultsADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45(dim) blast subtypes.ConclusionsThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- killer cells
- natural
- immunotherapy
- adoptive
- immunity
- innate
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Haroun-Izquierdo ...
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Vincenti, Marian ...
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Netskar, Herman
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van Ooijen, Hann ...
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Zhang, Bin
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Bendzick, Laura
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show more...
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Kanaya, Minoru
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Momayyezi, Pouri ...
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Li, Shuo
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Wiiger, Merete T ...
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Hoel, Hanna Juli ...
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Krokeide, Silje ...
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Kremer, Veronika
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Tjonnfjord, Geir
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Berggren, Stepha ...
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Wikström, Kristi ...
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Blomberg, Pontus
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Alici, Evren
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Felices, Martin
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Önfelt, Björn
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Höglund, Petter
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Valamehr, Bahram
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Ljunggren, Hans- ...
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Björklund, Andre ...
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Hammer, Quirin
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Kveberg, Lise
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Cichocki, Frank
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Miller, Jeffrey ...
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Malmberg, Karl-J ...
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Sohlberg, Ebba
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Cancer and Oncol ...
- Articles in the publication
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Journal for Immu ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet