Affordable Access

Publisher Website

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

Authors
  • Ghorashian, Sara1, 2
  • Lucchini, Giovanna3
  • Richardson, Rachel4
  • Nguyen, Kyvi4
  • Terris, Craig4
  • Guvenel, Aleks4
  • Oporto-Espuelas, Macarena4
  • Yeung, Jenny4
  • Pinner, Danielle3
  • Chu, Jan3
  • Williams, Lindsey3
  • Ko, Ka-Yuk3
  • Walding, Chloe5
  • Watts, Kelly6
  • Inglott, Sarah1
  • Thomas, Rebecca1
  • Connor, Christopher1
  • Adams, Stuart1
  • Gravett, Emma1
  • Gilmour, Kimberly7
  • And 22 more
  • 1 Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom. , (United Kingdom)
  • 2 Department of Developmental Biology and Cancer, University College London Great Ormond Street Institute of Child Health, London, United Kingdom. , (United Kingdom)
  • 3 Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom. , (United Kingdom)
  • 4 Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom. , (United Kingdom)
  • 5 Department of Haematology, University College London Hospital Trust, London, United Kingdom. , (United Kingdom)
  • 6 Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom. , (United Kingdom)
  • 7 Cell Therapy and Immunology Laboratory, Great Ormond Street Children's Hospital, London, United Kingdom. , (United Kingdom)
  • 8 Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom. , (United Kingdom)
  • 9 Autolus Ltd, London, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Jan 11, 2024
Volume
143
Issue
2
Pages
118–123
Identifiers
DOI: 10.1182/blood.2023020621
PMID: 37647647
Source
Medline
Language
English
License
Unknown

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 rate CD19 CAR (AUTO1) combined with a novel CD22 CAR capable of effective signaling at low antigen density. Twelve patients with advanced B-cell acute lymphoblastic leukemia were treated (CARPALL [Immunotherapy with CD19/22 CAR Redirected T Cells for High Risk/Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia] 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. Of 12 patients, 10 (83%) achieved a measurable residual disease (MRD)-negative complete remission at 2 months after infusion. Of 10 responding patients, 5 had emergence of MRD (n = 2) or relapse (n = 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% confidence interval [CI], 41%-91%) at 6 and 12 months. The 6- and 12-month event-free survival rates were 75% (95% CI, 41%-91%) and 60% (95% CI, 23%-84%), respectively. These data suggest dual targeting with cotransduction may prevent antigen-negative relapse after CAR T-cell therapy. © 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Report this publication

Statistics

Seen <100 times