학술논문
CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL.
Document Type
Academic Journal
Author
Ghorashian S; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Department of Developmental Biology and Cancer, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Lucchini G; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Richardson R; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Nguyen K; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Terris C; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Guvenel A; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Oporto-Espuelas M; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Yeung J; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Pinner D; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Chu J; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Williams L; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Ko KY; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Walding C; Department of Haematology, University College London Hospital Trust, London, United Kingdom.; Watts K; Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom.; Inglott S; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Thomas R; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Connor C; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Adams S; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Gravett E; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Gilmour K; Cell Therapy and Immunology Laboratory, Great Ormond Street Children's Hospital, London, United Kingdom.; Lal A; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.; Kunaseelan S; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.; Popova B; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.; Lopes A; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.; Ngai Y; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.; Hackshaw A; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.; Kokalaki E; Autolus Ltd, London, United Kingdom.; Carulla MB; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Mullanfiroze K; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Lazareva A; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Pavasovic V; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Rao A; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Bartram J; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Vora A; Department of Haematology, Great Ormond Street Children's Hospital, London, United Kingdom.; Chiesa R; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Silva J; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Rao K; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.; Bonney D; Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom.; Wynn R; Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom.; Pule M; Autolus Ltd, London, United Kingdom.; Hough R; Department of Haematology, University College London Hospital Trust, London, United Kingdom.; Amrolia PJ; Department of Bone Marrow Transplantation, Great Ormond Street Children's Hospital, London, United Kingdom.; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
Subject
Language
English
Abstract
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.)
(© 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.)