tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], George Karavalakis[SUP] #[/SUP][SUP] 1 [/SUP], Efthymia Papadopoulou[SUP] #[/SUP][SUP] 2 [/SUP], Aliki Xochelli[SUP] 3 [/SUP], Zoi Bousiou[SUP] 1 [/SUP], Anastasios Vogiatzoglou[SUP] 2 [/SUP], Penelope-Georgia Papayanni[SUP] 1 4 [/SUP], Aphrodite Georgakopoulou[SUP] 1 4 [/SUP], Maria Giannaki[SUP] 1 [/SUP], Fani Stavridou[SUP] 1 [/SUP], Ioanna Vallianou[SUP] 1 [/SUP], Maria Kammenou[SUP] 1 [/SUP], Evangelia Varsamoudi[SUP] 1 [/SUP], Vasiliki Papadimitriou[SUP] 1 [/SUP], Chrysavgi Giannaki[SUP] 5 [/SUP], Maria Sileli[SUP] 6 [/SUP], Zoi Stergiouda[SUP] 7 [/SUP], Garyfallia Stefanou[SUP] 8 [/SUP], Georgia Kourlaba[SUP] 9 [/SUP], George Gounelas[SUP] 8 [/SUP], Maria Triantafyllidou[SUP] 1 [/SUP], Eleni Siotou[SUP] 1 [/SUP], Antonia Karaglani[SUP] 10 [/SUP], Eleni Zotou[SUP] 1 4 [/SUP], Georgia Chatzika[SUP] 3 [/SUP], Anna Boukla[SUP] 3 [/SUP], Apostolia Papalexandri[SUP] 1 [/SUP], Maria-Georgia Koutra[SUP] 1 [/SUP], Dimitra Apostolou[SUP] 11 [/SUP], Georgia Pitsiou[SUP] 12 [/SUP], Petros Morfesis[SUP] 13 [/SUP], Michalis Doumas[SUP] 14 [/SUP], Theodoros Κarampatakis[SUP] 15 [/SUP], Nikolaos Kapravelos[SUP] 6 [/SUP], Militsa Bitzani[SUP] 5 [/SUP], Maria Theodorakopoulou[SUP] 16 [/SUP], Eva Serasli[SUP] 2 [/SUP], Grigorios Georgolopoulos[SUP] 1 [/SUP], Ioanna Sakellari[SUP] 1 [/SUP], Asimina Fylaktou[SUP] 3 [/SUP], Stavros Tryfon[SUP] 2 [/SUP], Achilles Anagnostopoulos[SUP] 1 [/SUP], Evangelia Yannaki[SUP] 17 18 [/SUP]
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[SUP] 1 [/SUP], George Karavalakis[SUP] #[/SUP][SUP] 1 [/SUP], Efthymia Papadopoulou[SUP] #[/SUP][SUP] 2 [/SUP], Aliki Xochelli[SUP] 3 [/SUP], Zoi Bousiou[SUP] 1 [/SUP], Anastasios Vogiatzoglou[SUP] 2 [/SUP], Penelope-Georgia Papayanni[SUP] 1 4 [/SUP], Aphrodite Georgakopoulou[SUP] 1 4 [/SUP], Maria Giannaki[SUP] 1 [/SUP], Fani Stavridou[SUP] 1 [/SUP], Ioanna Vallianou[SUP] 1 [/SUP], Maria Kammenou[SUP] 1 [/SUP], Evangelia Varsamoudi[SUP] 1 [/SUP], Vasiliki Papadimitriou[SUP] 1 [/SUP], Chrysavgi Giannaki[SUP] 5 [/SUP], Maria Sileli[SUP] 6 [/SUP], Zoi Stergiouda[SUP] 7 [/SUP], Garyfallia Stefanou[SUP] 8 [/SUP], Georgia Kourlaba[SUP] 9 [/SUP], George Gounelas[SUP] 8 [/SUP], Maria Triantafyllidou[SUP] 1 [/SUP], Eleni Siotou[SUP] 1 [/SUP], Antonia Karaglani[SUP] 10 [/SUP], Eleni Zotou[SUP] 1 4 [/SUP], Georgia Chatzika[SUP] 3 [/SUP], Anna Boukla[SUP] 3 [/SUP], Apostolia Papalexandri[SUP] 1 [/SUP], Maria-Georgia Koutra[SUP] 1 [/SUP], Dimitra Apostolou[SUP] 11 [/SUP], Georgia Pitsiou[SUP] 12 [/SUP], Petros Morfesis[SUP] 13 [/SUP], Michalis Doumas[SUP] 14 [/SUP], Theodoros Κarampatakis[SUP] 15 [/SUP], Nikolaos Kapravelos[SUP] 6 [/SUP], Militsa Bitzani[SUP] 5 [/SUP], Maria Theodorakopoulou[SUP] 16 [/SUP], Eva Serasli[SUP] 2 [/SUP], Grigorios Georgolopoulos[SUP] 1 [/SUP], Ioanna Sakellari[SUP] 1 [/SUP], Asimina Fylaktou[SUP] 3 [/SUP], Stavros Tryfon[SUP] 2 [/SUP], Achilles Anagnostopoulos[SUP] 1 [/SUP], Evangelia Yannaki[SUP] 17 18 [/SUP]
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.