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A Genetically Engineered Primary Human Natural Killer Cell Platform for Cancer Immunotherapy.
Pomeroy, Emily J; Hunzeker, John T; Kluesner, Mitchell G; Lahr, Walker S; Smeester, Branden A; Crosby, Margaret R; Lonetree, Cara-Lin; Yamamoto, Kenta; Bendzick, Laura; Miller, Jeffrey S; Geller, Melissa A; Walcheck, Bruce; Felices, Martin; Webber, Beau R; Starr, Timothy K; Moriarity, Branden S.
Afiliação
  • Pomeroy EJ; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Hunzeker JT; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Kluesner MG; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Lahr WS; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Smeester BA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Crosby MR; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Lonetree CL; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Yamamoto K; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
  • Bendzick L; Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Miller JS; Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
  • Geller MA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Walcheck B; Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55455, USA.
  • Felices M; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
  • Webber BR; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Starr TK; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Moriarity BS; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: mori0164@umn.edu.
Mol Ther ; 28(1): 52-63, 2020 01 08.
Article em En | MEDLINE | ID: mdl-31704085
Enhancing natural killer (NK) cell cytotoxicity by blocking inhibitory signaling could lead to improved NK-based cancer immunotherapy. Thus, we have developed a highly efficient method for editing the genome of human NK cells using CRISPR/Cas9 to knock out inhibitory signaling molecules. Our method efficiently edits up to 90% of primary peripheral blood NK cells. As a proof-of-principle we demonstrate highly efficient knockout of ADAM17 and PDCD1, genes that have a functional impact on NK cells, and demonstrate that these gene-edited NK cells have significantly improved activity, cytokine production, and cancer cell cytotoxicity. Furthermore, we were able to expand cells to clinically relevant numbers, without loss of activity. We also demonstrate that our CRISPR/Cas9 method can be used for efficient knockin of genes by delivering homologous recombination template DNA using recombinant adeno-associated virus serotype 6 (rAAV6). Our platform represents a feasible method for generating engineered primary NK cells as a universal therapeutic for cancer immunotherapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Células Matadoras Naturais / Engenharia Genética / Transferência Adotiva / Engenharia Celular Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Células Matadoras Naturais / Engenharia Genética / Transferência Adotiva / Engenharia Celular Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article