A phase I/II study of adoptive SARS-CoV-2-specific T cells in immunocompromised hosts with or at risk of severe COVID-19 infection.

Autor: Seng MS; Department of Paediatric Hematology and Oncology, KK Women's and Children's Hospital, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore., Ng KP; Department of Paediatric Hematology and Oncology, KK Women's and Children's Hospital, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore., Soh TG; Department of Hematology, National University Hospital, Singapore, Singapore., Tan TT; Duke-NUS Medical School, Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore., Chan M; HLA Laboratory, Health Sciences Authority, Singapore, Singapore., Maiwald M; Duke-NUS Medical School, Singapore, Singapore; Department of Pathology and Laboratory Medicine, Microbiology Service, KK Women's and Children's Hospital, Singapore, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tan LK; Department of Hematology, National University Hospital, Singapore, Singapore., Linn YC; Duke-NUS Medical School, Singapore, Singapore; Department of Hematology, Singapore General Hospital, Singapore, Singapore., Leung W; Department of Paediatric Hematology and Oncology, KK Women's and Children's Hospital, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore. Electronic address: leung.wing.hang@kkh.com.sg.
Jazyk: angličtina
Zdroj: Cytotherapy [Cytotherapy] 2024 Oct; Vol. 26 (10), pp. 1170-1178. Date of Electronic Publication: 2024 May 18.
DOI: 10.1016/j.jcyt.2024.05.014
Abstrakt: Background: Post-transplant or hematological cancer patients have a higher risk of mortality after infection with ancestral and early variants of severe acute respiratory syndrome (SARS)-CoV-2. Adoptive cell therapy (ACT) with virus-specific T cells (VSTs) could augment endogenous T cell immunity to avoid disease deterioration before viral clearance.
Methods: We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors. In a phase I/II study (NCT04457726), 13 adult and pediatric patients, acutely positive for SARS-CoV-2 and predicted to have a high chance of mortality, were recruited from September 2021 to February 2022. Twelve patients received a single dose of COVID-T cells, matched on at least 1 HLA.
Results: A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m 2 SARS-COV-2-specific T cells did not cause cytokine release syndrome, acute respiratory distress syndrome, or graft-versus-host disease. In the 8 patients who had detectable donor SARS-COV-2-specific T cells after ACT, none progressed to severe disease or died with COVID-19. In contrast, among the other four patients without evidence of donor micro-chimerism, two died of COVID-19.
Conclusions: Long-acting third-party VSTs from convalescent or vaccinated donors could be expediently produced and might be clinically useful in future pandemics, particularly before global vaccination is implemented.
Competing Interests: Declaration of competing interest W.L. is a part-time employee of Miltenyi Biotec. All authors declare no competing financial interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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