ArticleBlood advances2020
Large-scale GMP-compliant CRISPR-Cas9-mediated deletion of the glucocorticoid receptor in multivirus-specific T cells.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Cellular Therapies in Transplantation - Regulatory T Cell Therapies and Virus Specific Therapies.Current transplantation reports · 2025Article
- Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- Article
- GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Review
- CRISPR/Cas9 deletion of MIR155HG in human T cells reduces incidence and severity of acute GVHD in a xenogeneic model.Blood advances · 2024Article
- Combining different CRISPR nucleases for simultaneous knock-in and base editing prevents translocations in multiplex-edited CAR T cells.Genome biology · 2023Article
- Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond.HemaSphere · 2023Review
- Human iPS Cells for Clinical Applications and Cellular Products.Handbook of experimental pharmacology · 2023Article
- Nanomaterial-assisted CRISPR gene-engineering - A hallmark for triple-negative breast cancer therapeutics advancement.Materials today. Bio · 2022Review
- Enzymatically produced piggyBac transposon vectors for efficient non-viral manufacturing of CD19-specific CAR T cells.Molecular therapy. Methods & clinical development · 2021Article
- Review
- Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges.International journal of molecular sciences · 2021Review
- Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy.Cell reports · 2021Article
- Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art.Journal of fungi (Basel, Switzerland) · 2021Review
- CRISPR-Cas9-Edited Tacrolimus-Resistant Antiviral T Cells for Advanced Adoptive Immunotherapy in Transplant Recipients.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Harnessing T Cells to Control Infections After Allogeneic Hematopoietic Stem Cell Transplantation.Frontiers in immunology · 2020Review
- "Cerberus" T Cells: A Glucocorticoid-Resistant, Multi-Pathogen Specific T Cell Product to Fight Infections in Severely Immunocompromised Patients.Frontiers in immunology · 2020Article
- Super-Treg: Toward a New Era of Adoptive Treg Therapy Enabled by Genetic Modifications.Frontiers in immunology · 2020Review
- Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
38 authors.
Funding
Abstract
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.
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Registered trials
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