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CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL

Ghorashian, Sara; Lucchini, Giovanna; Richardson, Rachel; Nguyen, Kyvi; Terris, Craig; Guvenel, Aleks; Oporto Espuelas, Macarena; ... Amrolia, Persis J; + view all (2023) CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL. Blood 10.1182/blood.2023020621. (In press).

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Abstract

CD19-negative relapse is a leading cause of treatment failure after Chimeric antigen receptor (CAR) T-cell therapy for ALL. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral co-transduction with vectors encoding our previously-described fast-off rate CD19CAR (AUTO1) combined with a novel CD22CAR capable of effective signalling at low antigen density. Twelve patients with advanced B-ALL were treated (CARPALL study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Ten of 12 patients (83%) achieved a Measurable Residual Disease (MRD) negative complete remission at 2 months post infusion. Of 10 responding patients, 5 had emergence of MRD (2) or relapse (3) with CD19 and CD22 expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95%CI: 41-91%) at 6 and 12 months. Six and 12-month event free survival (EFS) were 75% (95%CI: 41-91%) and 60% (95%CI: 23-84%). These data suggest dual targeting with co-transduction may prevent antigen negative relapse after CAR T-cell therapy.

Type: Article
Title: CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL
Location: United States
DOI: 10.1182/blood.2023020621
Publisher version: https://doi.org/10.1182/blood.2023020621
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10177820
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