Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
Department of Respiratory Medicine, George Papanikolaou Hospital, Thessaloniki, Greece.
Nat Med. 2023 Aug;29(8):2019-2029. doi: 10.1038/s41591-023-02480-8. Epub 2023 Jul 17.
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 .
尽管取得了进展，但在严重的 2019 年冠状病毒病（COVID-19）中，很少有治疗方法显示出疗效。在另一种情况下，病毒特异性 T 细胞已被证明是安全有效的。我们进行了一项随机（2:1）、开放性、1/2 期试验，以评估在德尔塔变异为主时，与标准治疗（SoC）相比，使用现成的、部分人类白细胞抗原（HLA）匹配的、恢复期供体来源的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性 T 细胞（CoV-2-ST）联合 SoC 在严重 COVID-19 患者中的安全性和疗效。在剂量递增的 1 期安全性研究后，90 名参与者被随机分为接受 CoV-2-ST+SoC（n=60）或仅接受 SoC（n=30）。该研究的主要复合终点是恢复时间和 30 天恢复率的组合，以及接受 CoV-2-ST+SoC 的患者中 CoV-2-ST 的体内扩增与仅接受 SoC 的患者相比。关键次要终点是第 60 天的存活率。CoV-2-ST+SoC 治疗安全且耐受良好。该研究达到了主要复合终点（CoV-2-ST+SoC 与 SoC：恢复率分别为 65%和 38%，P=0.017；中位恢复时间分别为 11 天和未达到，P=0.052；恢复率比为 1.71（95%置信区间为 1.03-2.83，P=0.036））和与 SoC 相比 CoV-2-ST 显著扩增的共同主要终点（CoV-2-ST+SoC 与 SoC，P=0.047）。总的来说，在患有严重 COVID-19 的住院患者中，采用 CoV-2-ST 的过继免疫疗法是可行且安全的。需要更大规模的试验来加强严重 COVID-19 临床获益的初步证据。EudraCT 标识符：2021-001022-22。
