BE CAR33 T / Great Ormond Street Hospital for Children - LARVOL DELTA

A phase 1 feasibility trial of BE-CAR33, an "off-the-shelf" base-edited CAR33 T cell therapy for acute myeloid leukemia. (PubMed, Sci Transl Med) - "Participants received fludarabine, cyclophosphamide, and alemtuzumab followed by 1.2 to 1.8 × 106 BE-CAR33 cells per kilogram. Differentially expressed genes included editing signatures and switched from manufacturing-related toward postexpansion effector and exhaustion profiles. Although primary end points were not met, this first-in-human study demonstrated the feasibility of an "off-the-shelf" base-edited CAR T cell approach and informs future multiantigen strategies against AML."

First-in-human • IO biomarker • Journal • P1 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD52 • CD7

CARAML: Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2025 ➔ Jun 2026

Enrollment closed • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33

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

CARAML: Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33

CARAML: Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

CAR T-Cell Therapy • New P1 trial • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33