학술논문
Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.
Document Type
Academic Journal
Author
Peggs KS; Department of Hematology, University College London Hospital, London, UK.; Albon SJ; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Oporto Espuelas M; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK. Electronic address: m.oporto@ucl.ac.uk.; Irving C; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Richardson R; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Casanovas-Company J; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Wallace R; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK; Molecular Hematology Section, University College London Great Ormond Street Institute of Child Health, London, UK.; Guvenel A; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Ghorashian S; Molecular Hematology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Department of Hematology, Great Ormond Street Hospital for Children, London, UK.; Collura A; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Subramaniyam M; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK.; Flutter B; Gene and Cell Therapy, Great Ormond Street Hospital for Children, London, UK; Molecular Hematology Section, University College London Great Ormond Street Institute of Child Health, London, UK.; Popova B; Cancer Research UK and University College London Cancer Trials Center, London, UK.; Castro F; Cancer Research UK and University College London Cancer Trials Center, London, UK.; Lopes A; Cancer Research UK and University College London Cancer Trials Center, London, UK.; Champion K; Cancer Research UK and University College London Cancer Trials Center, London, UK.; Schofield O; Cancer Research UK and University College London Cancer Trials Center, London, UK.; Clifton-Hadley L; Cancer Research UK and University College London Cancer Trials Center, London, UK.; Taylor T; Department of Hematology, University College London Hospital, London, UK.; Farrell M; Department of Hematology, Manchester Royal Infirmary, Manchester, UK.; Adams S; Department of Hematology, Great Ormond Street Hospital for Children, London, UK.; Gilmour KC; Cell Therapy and Immunology, Camelia Botnar Laboratories, Great Ormond Street Hospital for Children, London, UK.; Mackinnon S; Department of Hematology, University College London Hospital, London, UK.; Tholouli E; Department of Hematology, Manchester Royal Infirmary, Manchester, UK.; Amrolia PJ; Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, UK. Electronic address: persis.amrolia@gosh.nhs.uk.
Source
Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE
Subject
Language
English
Abstract
Background Aims: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies.
Methods: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm.
Results: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively.
Conclusions: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.
Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article.
(Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
Methods: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm.
Results: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively.
Conclusions: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.
Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article.
(Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)