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Large-scale GMP-compliant CRISPR-Cas9-mediated deletion of the glucocorticoid receptor in multivirus-specific T cells.
Basar, Rafet; Daher, May; Uprety, Nadima; Gokdemir, Elif; Alsuliman, Abdullah; Ensley, Emily; Ozcan, Gonca; Mendt, Mayela; Hernandez Sanabria, Mayra; Kerbauy, Lucila Nassif; Nunez Cortes, Ana Karen; Li, Li; Banerjee, Pinaki P; Muniz-Feliciano, Luis; Acharya, Sunil; Fowlkes, Natalie W; Lu, Junjun; Li, Sufang; Mielke, Stephan; Kaplan, Mecit; Nandivada, Vandana; Bdaiwi, Mustafa; Kontoyiannis, Alexander D; Li, Ye; Liu, Enli; Ang, Sonny; Marin, David; Brunetti, Lorenzo; Gundry, Michael C; Turk, Rolf; Schubert, Mollie S; Rettig, Garrett R; McNeill, Matthew S; Kurgan, Gavin; Behlke, Mark A; Champlin, Richard; Shpall, Elizabeth J; Rezvani, Katayoun.
Afiliação
  • Basar R; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Daher M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Uprety N; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Gokdemir E; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Alsuliman A; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Ensley E; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Ozcan G; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Mendt M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Hernandez Sanabria M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Kerbauy LN; Department of Stem Cell Transplantation and Cellular Therapy, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
  • Nunez Cortes AK; Human Genome and Stem Cell Research Center, Biosciences Institute, Department of Genetics and Evolutionary Biology, University of Sao Paulo, Sao Paulo, Brazil.
  • Li L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Banerjee PP; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Muniz-Feliciano L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Acharya S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Fowlkes NW; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Lu J; Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Li S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Mielke S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Kaplan M; Cellterapi och Allogen Stamcellstransplantation, Department of Laboratory Medicine, Karolinska University Hospital and Institute, Stockholm, Sweden.
  • Nandivada V; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Bdaiwi M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Kontoyiannis AD; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Li Y; Harvard Medical School, Harvard University, Cambridge, MA.
  • Liu E; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Ang S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Marin D; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Brunetti L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Gundry MC; Center for Cell and Gene Therapy and.
  • Turk R; The Stem Cells and Regenerative Medicine Center, College of Medicine, Baylor University, Houston, TX; and.
  • Schubert MS; Center for Cell and Gene Therapy and.
  • Rettig GR; The Stem Cells and Regenerative Medicine Center, College of Medicine, Baylor University, Houston, TX; and.
  • McNeill MS; Integrated DNA Technologies, Coralville, IA.
  • Kurgan G; Integrated DNA Technologies, Coralville, IA.
  • Behlke MA; Integrated DNA Technologies, Coralville, IA.
  • Champlin R; Integrated DNA Technologies, Coralville, IA.
  • Shpall EJ; Integrated DNA Technologies, Coralville, IA.
  • Rezvani K; Integrated DNA Technologies, Coralville, IA.
Blood Adv ; 4(14): 3357-3367, 2020 07 28.
Article em En | MEDLINE | ID: mdl-32717029
Virus-specific T cells have proven highly effective for the treatment of severe and drug-refractory infections after hematopoietic stem cell transplant (HSCT). However, the efficacy of these cells is hindered by the use of glucocorticoids, often given to patients for the management of complications such as graft-versus-host disease. To address this limitation, we have developed a novel strategy for the rapid generation of good manufacturing practice (GMP)-grade glucocorticoid-resistant multivirus-specific T cells (VSTs) using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing technology. We have shown that deleting the nuclear receptor subfamily 3 group C member 1 (NR3C1; the gene encoding for the glucocorticoid receptor) renders VSTs resistant to the lymphocytotoxic effect of glucocorticoids. NR3C1-knockout (KO) VSTs kill their targets and proliferate successfully in the presence of high doses of dexamethasone both in vitro and in vivo. Moreover, we developed a protocol for the rapid generation of GMP-grade NR3C1 KO VSTs with high on-target activity and minimal off-target editing. These genetically engineered VSTs promise to be a novel approach for the treatment of patients with life-threatening viral infections post-HSCT on glucocorticoid therapy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas / Sistemas CRISPR-Cas Tipo de estudo: Guideline Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas / Sistemas CRISPR-Cas Tipo de estudo: Guideline Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article