Sökning: id:"swepub:oai:DiVA.org:kth-228141" >
Intrinsic Functiona...
Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors
-
- Oei, Vincent Yi Sheng (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway.
-
- Siernicka, Marta (författare)
- Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland.;Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland.
-
- Graczyk-Jarzynka, Agnieszka (författare)
- Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland.
-
visa fler...
-
- Hoel, Hanna Julie (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
-
- Yang, Weiwen (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
-
- Palacios, Daniel (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway.
-
- Almasbak, Hilde (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
-
- Bajor, Malgorzata (författare)
- Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland.
-
- Clement, Dennis (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway.
-
- Brandt, Ludwig (författare)
- KTH,Science for Life Laboratory, SciLifeLab
-
- Önfelt, Björn (författare)
- Karolinska Institutet,KTH,Tillämpad fysik,Science for Life Laboratory, SciLifeLab,Karolinska Inst
-
- Goodridge, Jodie (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway.
-
- Winiarska, Magdalena (författare)
- Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland.
-
- Zagozdzon, Radoslaw (författare)
- Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland.;Med Univ Warsaw, Inst Transplantat, Dept Clin Immunol, Warsaw, Poland.
-
- Olweus, Johanna (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway.
-
- Kyte, Jon-Amund (författare)
- Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.;Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
-
- Malmberg, Karl-Johan (författare)
- Karolinska Institutet
-
visa färre...
-
Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway. Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland.;Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland. (creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2018
- 2018
- Engelska.
-
Ingår i: CANCER IMMUNOLOGY RESEARCH. - : AMER ASSOC CANCER RESEARCH. - 2326-6066 .- 2326-6074. ; 6:4, s. 467-480
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles. Kinetics experiments revealed that CAR expression was optimal after 3 days of IL15 stimulation prior to transfection, consistently achieving over 80% expression. CAR-engineered NK cells acquired increased degranulation toward CD19(+) targets, and maintained their intrinsic degranulation response toward CD19(-) K562 cells. The response of redirected NK-cell subsets against CD19(+) targets was dependent on their intrinsic thresholds for activation determined through both differentiation and education by killer cell immunoglobulin-like receptors (KIR) and/or CD94/NKG2A binding to self HLA class I and HLA-E, respectively. Redirected primary NK cells were insensitive to inhibition through NKG2A/HLA-E interactions but remained sensitive to inhibition through KIR depending on the amount of HLA class I expressed on target cells. Adaptive NK cells, expressing NKG2C, CD57, and self-HLA-specific KIR(s), displayed superior ability to kill CD19(+), HLA low, or mismatched tumor cells. These findings support the feasibility of primary allogeneic NK cells for CAR engineering and highlight a need to consider NK-cell diversity when optimizing efficacy of cancer immunotherapies based on CAR-expressing NK cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Oei, Vincent Yi ...
-
Siernicka, Marta
-
Graczyk-Jarzynka ...
-
Hoel, Hanna Juli ...
-
Yang, Weiwen
-
Palacios, Daniel
-
visa fler...
-
Almasbak, Hilde
-
Bajor, Malgorzat ...
-
Clement, Dennis
-
Brandt, Ludwig
-
Önfelt, Björn
-
Goodridge, Jodie
-
Winiarska, Magda ...
-
Zagozdzon, Rados ...
-
Olweus, Johanna
-
Kyte, Jon-Amund
-
Malmberg, Karl-J ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Cell och molekyl ...
- Artiklar i publikationen
-
CANCER IMMUNOLOG ...
- Av lärosätet
-
Kungliga Tekniska Högskolan
-
Karolinska Institutet