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11 results on '"Gkazi, Soragia Athina"'

2. Tvt CAR7: Phase 1 Clinical Trial of Base-Edited "Universal” CAR7 T Cells for Paediatric Relapsed/Refractory T-ALL

Author

Chiesa, Robert, primary, Georgiadis, Christos, additional, Ottaviano, Giorgio, additional, Syed, Farhatullah, additional, Braybrook, Toni, additional, Etuk, Annie, additional, Zhan, Hong, additional, Gkazi, Soragia Athina, additional, Preece, Roland, additional, Adams, Stuart, additional, Thomas, Rebecca, additional, Awuah, Arnold, additional, Gilmour, Kimberly, additional, Mhaldien, Lana, additional, Chu, Jan, additional, Pinner, Danielle, additional, Kubat, Agnieszka, additional, Veys, Paul, additional, Rao, Kanchan, additional, Lucchini, Giovanna, additional, O'Connor, David, additional, Vora, Ajay, additional, and Qasim, Waseem, additional

Published
2022
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3. Single and Combinational Multiplex Base-Edited 'Universal' CAR T Cells in a Humanised Model of Primary CD7+CD33+ AML

Author

Kloos, Arnold, primary, Georgiadis, Christos, additional, Etuk, Annie, additional, Gkazi, Soragia Athina, additional, Syed, Farhatullah, additional, Braybrook, Toni, additional, Zhan, Hong, additional, Kadirkamanathan, Renuka, additional, Kattre, Nadine, additional, Görlich, Kerstin, additional, Fangmann, Thomas, additional, Schambach, Axel, additional, Sauer, Martin G., additional, Heuser, Michael, additional, and Qasim, Waseem, additional

Published
2022
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5. TT52CAR19: Phase 1 Trial of CRISPR/Cas9 Edited Allogeneic CAR19 T Cells for Paediatric Relapsed/Refractory B-ALL

Author

Ottaviano, Giorgio, primary, Georgiadis, Christos, additional, Syed, Farhatullah, additional, Gkazi, Soragia Athina, additional, Zhan, Hong, additional, Etuk, Annie, additional, Chu, Jan, additional, Pinner, Danielle, additional, Inglott, Sarah, additional, Gilmour, Kimberly, additional, Adams, Stuart, additional, Kricke, Susanne, additional, Izotova, Natalia, additional, Ladon, Dariusz, additional, Kubat, Agnieszka, additional, Veys, Paul, additional, Vora, Ajay, additional, Rao, Kanchan, additional, and Qasim, Waseem, additional

Published
2021
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7. Bipotent Lymphoid Progenitors Independently Maintain Long-Term Genetically Engineered T and NK Cell Production in Humans

Author

Izotova, Natalia, primary, Rivat, Christine, additional, Baricordi, Cristina, additional, Blanco-Alvarez, Elena, additional, Pellin, Danilo, additional, Watt, Eleanor, additional, Gkazi, Soragia Athina, additional, Adams, Stuart, additional, Gilmour, Kimberly, additional, Bayford, Jinhua Xu, additional, Booth, Claire, additional, Gaspar, Bobby H, additional, Thrasher, Adrian J., additional, and Biasco, Luca, additional

Published
2020
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9. Cytosine Deaminase Base Editing to Restore COL7A1in Dystrophic Epidermolysis Bullosa Human: Murine Skin Model

Author

Naso, Gaetano, Gkazi, Soragia Athina, Georgiadis, Christos, Jayarajan, Vignesh, Jacków, Joanna, Fleck, Roland, Allison, Leanne, Ogunbiyi, Olumide Kayode, McGrath, John Alexander, Ilic, Dusko, Di, Wei-Li, Petrova, Anastasia, and Qasim, Waseem

Abstract

Recessive dystrophic epidermolysis bullosa is a debilitating blistering skin disorder caused by loss-of-function mutations in COL7A1,which encodes type VII collagen, the main component of anchoring fibrils at the dermal−epidermal junction. Although conventional gene therapy approaches through viral vectors have been tested in preclinical and clinical trials, they are limited by transgene size constraints and only support unregulated gene expression. Genome editing could potentially overcome some of these limitations, and CRISPR/Cas9 has already been applied in research studies to restore COL7A1expression. The delivery of suitable repair templates for the repair of DNA cleaved by Cas9 is still a major challenge, and alternative base editing strategies may offer corrective solutions for certain mutations. We show highly targeted and efficient cytidine deamination and molecular correction of a defined recessive dystrophic epidermolysis bullosa mutation (c.425A>G), leading to restoration of full-length type VII collagen protein expression in primary human fibroblasts and induced pluripotent stem cells. Type VII collagen basement membrane expression and skin architecture were restored with de novo anchoring fibrils identified by electron microscopy in base-edited human recessive dystrophic epidermolysis bullosa grafts recovered from immunodeficient mice. The results show the potential and promise of emerging base editing technologies in tackling inherited disorders with well-defined single nucleotide mutations.

Published
2023
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10. Umbilical cord blood T cells can be isolated and enriched by CD62L selection for use in 'off the shelf' chimeric antigen receptor T-cell therapies to widen transplant options.

Author

Georgiadis C, Nickolay L, Syed F, Zhan H, Gkazi SA, Etuk A, Abramowski-Mock U, Preece R, Cuber P, Adams S, Ottaviano G, and Qasim W

Abstract

Umbilical cord blood (UCB) T cells exhibit distinct naive ontogenetic profiles and may be an attractive source of starting cells for the production of chimeric antigen receptor (CAR) T cells. Pre-selection of UCB-T cells on the basis of CD62L expression was investigated as part of a machine-based manufacturing process, incorporating lentiviral transduction, CRISPR-Cas9 editing, T-cell expansion and depletion of residual TCReeeT cells. This provided stringent mitigation against the risk of graft versus host disease (GVHD), and was combined with simultaneous knockout of CD52 to enable persistence of edited T cells in combination with preparative lymphodepletion using Alemtuzumab. Under compliant manufacturing conditions, two cell banks were generated with high levels of CAR19 expression and minimal carriage of TCReeeT cells. Sufficient cells were cryopreserved in dose-banded aliquots at the end of each campaign to treat dozens of potential recipients. Molecular characterisation captured vector integration sites and CRISPR editing signatures and functional studies, including in vivo potency studies in humanised mice, confirmed antileukaemic activity comparable to peripheral blood-derived universal CAR19 T cells. Machine manufactured UCB derived T cells banks offer an alternative to autologous cell therapies and could help widen access to CAR T cells.

Published
2024
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11. CRISPR-Mediated Base Conversion Allows Discriminatory Depletion of Endogenous T Cell Receptors for Enhanced Synthetic Immunity.

Author

Preece R, Pavesi A, Gkazi SA, Stegmann KA, Georgiadis C, Tan ZM, Aw JYJ, Maini MK, Bertoletti A, and Qasim W

Abstract

Emerging base editing technology exploits CRISPR RNA-guided DNA modification effects for highly specific C > T conversion, which has been used to efficiently disrupt gene expression. These tools can enhance synthetic T cell immunity by restricting specificity, addressing histocompatibility leukocyte antigen (HLA) barriers, and promoting persistence. We report lentiviral delivery of a hepatitis B-virus (HBV)-specific recombinant T cell receptor (rTCR) and a linked CRISPR single-guide RNA for simultaneous disruption of endogenous TCRs (eTCRs) when combined with transient cytosine deamination. Discriminatory depletion of eTCR and coupled expression of rTCR resulted in enrichment of HBV-specific populations from 55% (SEM, ±2.4%) to 95% (SEM, ±0.5%). Intensity of rTCR expression increased 1.8- to 2.9-fold compared to that in cells retaining their competing eTCR, and increased cytokine production and killing of HBV antigen-expressing hepatoma cells in a 3D microfluidic model were exhibited. Molecular signatures confirmed that seamless conversion of C > T (G > A) had created a premature stop codon in TCR beta constant 1/2 loci, with no notable activity at predicted off-target sites. Thus, targeted disruption of eTCR by cytosine deamination and discriminatory enrichment of antigen-specific T cells offers the prospect of enhanced, more specific T cell therapies against HBV-associated hepatocellular carcinoma (HCC) as well as other viral and tumor antigens., (© 2020 The Authors.)

Published
2020
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