Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain.
Internal Medicine Department, Hospital de Emergencias Enfermera Isabel Zendal, Madrid, Spain.
Cytotherapy. 2024 Jan;26(1):25-35. doi: 10.1016/j.jcyt.2023.10.002. Epub 2023 Oct 29.
There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment.
Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 10/kg CD45RA memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA memory T cells and the most frequent human leukocyte antigen typing in the Spanish population.
We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events.
Adoptive cell therapy with off-the-shelf CD45RA memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia.
NCT04578210.
目前，对于低氧血症的 2019 年冠状病毒病（COVID-19）住院患者，尚无有效的抗病毒治疗方法。淋巴细胞减少是疾病严重程度的生物标志物，通常存在于住院患者中。必须考虑增加具有抗病毒作用的淋巴细胞的方法来治疗这些患者。在我们的 1 期研究之后，我们进行了一项 2 期随机多中心临床试验，评估了输注同种异体现成 CD45RA 记忆 T 细胞的疗效，这些 T 细胞包含来自恢复期供体的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性 T 细胞，外加标准治疗（SoC）与仅 SoC 治疗相比。
84 名患者在三个西班牙中心入组。患者被随机分为输注 1×10/kg CD45RA 记忆 T 细胞或 SoC。我们根据 CD45RA 记忆 T 细胞中干扰素 γ SARS-CoV-2 特异性反应和西班牙人群中最常见的人类白细胞抗原类型，从 4 名未接种疫苗的供体中选择。
我们分析了 81 名患者的数据。主要结局是恢复的比例，定义为每组中参与者的比例，其标准为发热正常、氧饱和度持续至少 24 小时以及淋巴细胞减少通过第 14 天或出院恢复。实验组达到了这一主要终点。我们还观察到实验组淋巴细胞恢复更快。我们没有观察到任何与治疗相关的不良事件。
使用含有 SARS-CoV-2 特异性 T 细胞的现成 CD45RA 记忆 T 细胞的过继细胞治疗是安全有效的，可以加速 COVID-19 肺炎和/或淋巴细胞减少症患者的淋巴细胞恢复。
NCT04578210。
