Danielle Pinner

A phase 1 feasibility trial of BE-CAR33, an “off-the-shelf” base-edited CAR33 T cell therapy for acute myeloid leukemia

Christos Georgiadis, Robert Chiesa, Hebatalla Rashed, Bethany K. Hughes et autres

Chimeric antigen receptor (CAR) T cell therapy for acute myeloid leukemia (AML) is constrained by antigen heterogeneity and shared expression with healthy compartments, and there are often challenges in obtaining autologous T cells from heavily pretreated patients. To address these challenges, we …

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Long-term outcomes of genome-edited “universal” CAR19 T cells for relapsed/refractory B-ALL at a single pediatric center

Daniela Guardo, Avijeet Kumar Mishra, Kimberly Gilmour, Stuart Adams et autres

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CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL

Sara Ghorashian, Giovanna Lucchini, Rachael T. Richardson, Kyvi Nguyen et autres

ABSTRACT: CD19-negative relapse is a leading cause of treatment failure after chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral cotransduction with vectors encoding our previously described fast-off …

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

Robert Chiesa, Christos Georgiadis, Giorgio Ottaviano, Farhatullah Syed et autres

Background Genome editing can overcome HLA barriers to generate 'off-the-shelf’ CAR T cell therapies. Despite the success of CAR-T cell therapies in B-cell malignancies, the expression of shared T cell antigens has constrained the development of CAR T cells targeting T-cell malignancies, …

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Dual Antigen Targeting with Co-Transduced CD19/22 CAR T Cells May Prevent Antigen-Negative Relapse after CAR T Cell Therapy for Relapsed/Refractory ALL

Sara Ghorashian, Giovanna Lucchini, Rachael T. Richardson, Kyvi Nguyen et autres

Background: CD19 negative escape is a major cause of relapse after CD19 CAR T cell therapy for relapsed/refractory (r/r) paediatric Acute Lymphoblastic Leukemia (ALL) and dual targeting of CD19/CD22 may overcome this. We have previously shown that AUTO1, a fast off rate …

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Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia

Giorgio Ottaviano, Christos Georgiadis, Soragia Athina Gkazi, Farhatullah Syed et autres

Genome editing of allogeneic T cells can provide “off-the-shelf” alternatives to autologous chimeric antigen receptor (CAR) T cell therapies. Disruption of T cell receptor α chain (TRAC) to prevent graft-versus-host disease (GVHD) and removal of CD52 (cluster of differentiation 52) for a …

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

Giorgio Ottaviano, Christos Georgiadis, Farhatullah Syed, Soragia Athina Gkazi et autres

Abstract Background 'Off-the-shelf' CAR T cell therapies are being investigated as alternatives to autologous CAR therapy, and can be generated using genome editing from allogeneic donors. Strategies to address HLA barriers include disruption of T cell receptor expression to prevent GVHD and …

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Therapy of Paediatric B-ALL with a Fast Off Rate CD19 CAR Leads to Enhanced Expansion and Prolonged CAR T Cell Persistence in Patients with Low Bone Marrow Tumour Burden, and Is Associated with a Favourable Toxicity Profile

Sara Ghorashian, Anne Marijn Kramer, Shimobi Onuoha, Gary Wright et autres

Introduction: The CARPALL study (NCT02443831) employed a novel CD19CAR (CAT-41BBz CAR) with a faster off rate than the Kymriah FMC63-41BBz CAR (CAT 3.1x10-3s-1, FMC 6.8 x 10-5s-1), with equivalent on-rate (CAT 2.2 x 105, FMC 2.1 x 105). We herein report updated …

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Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial

Robert Chiesa, Joseph F. Standing, Robert B. Winter, Zohreh Nademi et autres

Treosulfan is given off‐label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan‐fludarabine conditioning were followed for at least 1 year posttransplant. PKs were …

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Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR

Sara Ghorashian, Anne Marijn Kramer, Shimobi Onuoha, Gary Wright et autres

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A Novel Low Affinity CD19CAR Results in Durable Disease Remissions and Prolonged CAR T Cell Persistence without Severe CRS or Neurotoxicity in Patients with Paediatric ALL

Sara Ghorashian, Anne Marijn Kramer, Sarah J. Albon, Gary Wright et autres

Abstract Introduction: Published studies of CD19 CAR T cells have shown unprecedented response rates in ALL but with a 23-27% incidence of severe Cytokine Release Syndrome (CRS) and 27-50% incidence of severe neurotoxicity which may limit broader application. We developed a novel …

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Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

Waseem Qasim, Hong Zhan, Sujith Samarasinghe, Stuart Adams et autres

B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. …

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