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Nat Med
. 2023 Jul 17.
doi: 10.1038/s41591-023-02480-8. Online ahead of print. SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial
Anastasia Papadopoulou 1 , George Karavalakis # 1 , Efthymia Papadopoulou # 2 , Aliki Xochelli 3 , Zoi Bousiou 1 , Anastasios Vogiatzoglou 2 , Penelope-Georgia Papayanni 1 4 , Aphrodite Georgakopoulou 1 4 , Maria Giannaki 1 , Fani Stavridou 1 , Ioanna Vallianou 1 , Maria Kammenou 1 , Evangelia Varsamoudi 1 , Vasiliki Papadimitriou 1 , Chrysavgi Giannaki 5 , Maria Sileli 6 , Zoi Stergiouda 7 , Garyfallia Stefanou 8 , Georgia Kourlaba 9 , George Gounelas 8 , Maria Triantafyllidou 1 , Eleni Siotou 1 , Antonia Karaglani 10 , Eleni Zotou 1 4 , Georgia Chatzika 3 , Anna Boukla 3 , Apostolia Papalexandri 1 , Maria-Georgia Koutra 1 , Dimitra Apostolou 11 , Georgia Pitsiou 12 , Petros Morfesis 13 , Michalis Doumas 14 , Theodoros Κarampatakis 15 , Nikolaos Kapravelos 6 , Militsa Bitzani 5 , Maria Theodorakopoulou 16 , Eva Serasli 2 , Grigorios Georgolopoulos 1 , Ioanna Sakellari 1 , Asimina Fylaktou 3 , Stavros Tryfon 2 , Achilles Anagnostopoulos 1 , Evangelia Yannaki 17 18
Affiliations
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.
. 2023 Jul 17.
doi: 10.1038/s41591-023-02480-8. Online ahead of print. SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial
Anastasia Papadopoulou 1 , George Karavalakis # 1 , Efthymia Papadopoulou # 2 , Aliki Xochelli 3 , Zoi Bousiou 1 , Anastasios Vogiatzoglou 2 , Penelope-Georgia Papayanni 1 4 , Aphrodite Georgakopoulou 1 4 , Maria Giannaki 1 , Fani Stavridou 1 , Ioanna Vallianou 1 , Maria Kammenou 1 , Evangelia Varsamoudi 1 , Vasiliki Papadimitriou 1 , Chrysavgi Giannaki 5 , Maria Sileli 6 , Zoi Stergiouda 7 , Garyfallia Stefanou 8 , Georgia Kourlaba 9 , George Gounelas 8 , Maria Triantafyllidou 1 , Eleni Siotou 1 , Antonia Karaglani 10 , Eleni Zotou 1 4 , Georgia Chatzika 3 , Anna Boukla 3 , Apostolia Papalexandri 1 , Maria-Georgia Koutra 1 , Dimitra Apostolou 11 , Georgia Pitsiou 12 , Petros Morfesis 13 , Michalis Doumas 14 , Theodoros Κarampatakis 15 , Nikolaos Kapravelos 6 , Militsa Bitzani 5 , Maria Theodorakopoulou 16 , Eva Serasli 2 , Grigorios Georgolopoulos 1 , Ioanna Sakellari 1 , Asimina Fylaktou 3 , Stavros Tryfon 2 , Achilles Anagnostopoulos 1 , Evangelia Yannaki 17 18
Affiliations
- PMID: 37460756
- DOI: 10.1038/s41591-023-02480-8
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.