BE CAR7 T / Great Ormond Street Hospital for Children - LARVOL DELTA

Universal base-edited CAR7 T cells for T-cell acute lymphoblastic leukemia (ASH 2025) - "BE-CAR7 T cells were infused afterlymphodepletion (LD) with fludarabine (150 mg per square meter), cyclophosphamide (120 mg/kg) andalemtuzumab (1 mg/kg). As anticipated, viral reactivations were frequent, and three patientsexperienced significant virus-related morbidity post-transplant. Overall, 7/11 (63%) subjects dosed werein ongoing remission 3-36 months after transplant, and suspected CD7 negative leukemic escape hasbeen documented in 2 patients.Conclusions Universal BE-CAR7 T cells offer the prospect of leukemic remission for patients with CD7+ r/rT-ALL ahead of allo-SCT and will be further assessed in children and adults in extended cohorts."

Acute Lymphocytic Leukemia • Bone Marrow Transplantation • CNS Disorders • Dermatology • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD52 • CD7

Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia. (PubMed, N Engl J Med) - "Universal BE-CAR7 T cells induced leukemic remission in patients with relapsed or refractory T-cell ALL, thus allowing successful allogeneic hematopoietic stem-cell transplantation in most of the patients. (Funded by the Medical Research Council and others; ISRCTN Registry number, ISRCTN15323014.)."

Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Palliative care • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • CD52

Base edited CAR T cells for combinatorial strategies against acute myeloid leukaemia (ESGCT 2024) - "Base edited “universal” TCRa/b- CD7- CD52- BE-CARCLL-1, BE-CAR33 and BE-CAR7 effectors were generated from peripheral blood mononuclear cells by lentiviral transduction following activation, and electroporation with base-editor mRNA alongside multiplexed base editing single guide RNAs...Disruption of CD7 was included to enable BE-CAR7 production and allow co-infusion of other BE-CAR products, and CD52 editing conferred resistance to Alemtuzumab...Therapeutic strategies envisage ‘pick & mix’ applications of universal CAR T cell combinations determined by patient-specific target selection after flow-based disease immunophenotyping. Combinations of fratricide-resistant, lymphodepletion insensitive, co-infusion compatible CAR T cells would be harnessed for leukaemic eradication and deep preparative conditioning ahead of programmed, donor-derived reconstitution following allogeneic haematopoietic stem cell transplant (HSCT)."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD33

Base edited "universal" donor CAR T-cell strategies for acute myeloid leukaemia. (PubMed, Leukemia) - "We also demonstrate that removal of shared CD7 antigens enabled compatibility of BE-CAR33 and BE-CARCLL-1 with BE-CAR7 T cells, including in a patient-derived xenograft (PDX) model of AML. Therapeutic strategies envisage 'pick and mix' applications of base edited "universal" CAR T cells in combination determined by patient-specific antigen profiles. Such approaches also offer the possibility of deep, cell-based, de-bulking and conditioning ahead of allo-SCT and subsequent donor-derived reconstitution."

IO biomarker • Journal • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33

CRISPR-Cas9 Therapies in Hematologic Malignancies: A Meta-Analysis of Clinical Outcomes, Safety, and Translational Implications (SOHO 2025) - "Base-edited CAR7 T cells achieved CR in five of nine pediatric T-ALL patients... CRISPR-Cas9-based therapies exhibit promising antitumor activity and a manageable safety profile in hematologic cancers. These findings support the clinical viability of gene-edited cellular therapy, especially in relapsed settings. However, larger trials and long-term data are essential to validate the durability, genomic stability, and scalability of these platforms."

Clinical data • Retrospective data • Acute Lymphocytic Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD7 • PD-1

Combinational "Off-the-Shelf' CAR T Cells: A Unified Front Against AML Heterogeneity (ASGCT 2025) - "We generated 'universal', TCRαβ depleted BE-CAR7, BE-CAR33 and BE-CARCLL-1 CAR T cells and evaluated their application against highly heterogeneous and aggressive AML...Pre-manufactured and ready to use allogeneic combinations should enable timely interventions against AML where disease can otherwise evolve and progress rapidly. Disease Focus of Abstract:Cancer Hematologic"

CAR T-Cell Therapy • Heterogeneity • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Glomerulonephritis • Graft versus Host Disease • Immunology • B2M • CD33 • CD52 • CD7 • CD70

Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust | Trial completion date: Sep 2024 ➔ Feb 2025

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD7

Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia. (PubMed, N Engl J Med) - "The interim results of this phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia and indicate the anticipated risks of immunotherapy-related complications. (Funded by the Medical Research Council and others; ISRCTN number, ISRCTN15323014.)."

Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • CD52 • CD7

Tvt CAR7: Phase 1 Clinical Trial of Base-Edited "Universal" CAR7 T Cells for Paediatric Relapsed/Refractory T-ALL (ASH 2022) - "Eligible patients receive lymphodepletion with fludarabine (150 mg/sqm), cyclophosphamide (120 mg/kg) and alemtuzumab (1 mg/kg), followed by infusion of 0.2-2.0x106 BE-CAR7 T cells (maximum 5x104/kg TCRαβ T cells). This Phase 1 study aims to treat 10 children in the UK. Conclusion The study has demonstrated the feasibility of manufacturing "off-the-shelf" GMP-compliant base edited CAR7 T cells and is investigating their safety and efficacy against paediatric r/r T-ALL."

Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • Gene Therapies • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Transplantation • CD52 • CD7

Single and Combinational Multiplex Base-Edited 'Universal' CAR T Cells in a Humanised Model of Primary CD7+CD33+ AML (ASH 2022) - "Lentiviral transduction and multiplexed base editing to remove TCR, CD52 and the shared AML/T lineage antigen CD7, enabled the generation of universal donor CAR T cells for combinational use. This data demonstrates robust activity of BE-CAR33 alone and in combination with BE-CAR7 against human CD7+CD33+AML in mice and highlights the importance of strategies that ensure complete targeting of leukemic populations."

CAR T-Cell Therapy • IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD2 • CD33 • CD52 • CD7 • HAVCR2 • KIT • LAG3 • PD-1 • PD-L1 • PTPRC

Study of Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

New P1 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD7