학술논문
SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial
Document Type
Original Paper
Author
Papadopoulou, Anastasia; Karavalakis, George; Papadopoulou, Efthymia; Xochelli, Aliki; Bousiou, Zoi; Vogiatzoglou, Anastasios; Papayanni, Penelope-Georgia; Georgakopoulou, Aphrodite; Giannaki, Maria; Stavridou, Fani; Vallianou, Ioanna; Kammenou, Maria; Varsamoudi, Evangelia; Papadimitriou, Vasiliki; Giannaki, Chrysavgi; Sileli, Maria; Stergiouda, Zoi; Stefanou, Garyfallia; Kourlaba, Georgia; Gounelas, George; Triantafyllidou, Maria; Siotou, Eleni; Karaglani, Antonia; Zotou, Eleni; Chatzika, Georgia; Boukla, Anna; Papalexandri, Apostolia; Koutra, Maria-Georgia; Apostolou, Dimitra; Pitsiou, Georgia; Morfesis, Petros; Doumas, Michalis; Karampatakis, Theodoros; Kapravelos, Nikolaos; Bitzani, Militsa; Theodorakopoulou, Maria; Serasli, Eva; Georgolopoulos, Grigorios; Sakellari, Ioanna; Fylaktou, Asimina; Tryfon, Stavros; Anagnostopoulos, Achilles; Yannaki, Evangelia
Source
Nature Medicine. 29(8):2019-2029
Subject
Language
English
ISSN
1078-8956
1546-170X
1546-170X
Abstract
Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03–2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22.
Adoptive transfer of convalescent donor-derived SARS-CoV-2-specific T cells was safe and conferred faster recovery in patients with severe COVID-19 compared to standard of care.
Adoptive transfer of convalescent donor-derived SARS-CoV-2-specific T cells was safe and conferred faster recovery in patients with severe COVID-19 compared to standard of care.