Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom.
National Microbiological Reference Unit, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom.
Front Immunol. 2021 Jan 8;11:598402. doi: 10.3389/fimmu.2020.598402. eCollection 2020.
COVID-19 disease caused by the SARS-CoV-2 virus is characterized by dysregulation of effector T cells and accumulation of exhausted T cells. T cell responses to viruses can be corrected by adoptive cellular therapy using donor-derived virus-specific T cells. One approach is the establishment of banks of HLA-typed virus-specific T cells for rapid deployment to patients. Here we show that SARS-CoV-2-exposed blood donations contain CD4 and CD8 memory T cells which recognize SARS-CoV-2 spike, nucleocapsid and membrane antigens. Peptides of these antigens can be used to isolate virus-specific T cells in a GMP-compliant process. The isolated T cells can be rapidly expanded using GMP-compliant reagents for use as an allogeneic therapy. Memory and effector phenotypes are present in the selected virus-specific T cells, but our method rapidly expands the desirable central memory phenotype. A manufacturing yield ranging from 10 to 10 T cells can be obtained within 21 days culture. Thus, multiple therapeutic doses of virus-specific T cells can be rapidly generated from convalescent donors for potential treatment of COVID-19 patients.
由 SARS-CoV-2 病毒引起的 COVID-19 疾病的特征是效应 T 细胞失调和耗竭 T 细胞的积累。通过使用供体来源的病毒特异性 T 细胞进行过继细胞治疗，可以纠正针对病毒的 T 细胞反应。一种方法是建立 HLA 配型病毒特异性 T 细胞库，以便快速部署到患者。在这里，我们表明，暴露于 SARS-CoV-2 的血液供体中含有识别 SARS-CoV-2 刺突、核衣壳和膜抗原的 CD4 和 CD8 记忆 T 细胞。这些抗原的肽可用于在符合 GMP 的过程中分离病毒特异性 T 细胞。使用符合 GMP 的试剂可以快速扩增分离的 T 细胞，作为同种异体治疗。在选定的病毒特异性 T 细胞中存在记忆和效应表型，但我们的方法可以快速扩增所需的中央记忆表型。在 21 天的培养过程中，可以获得 10 到 10 的 T 细胞的制造产量。因此，可以从恢复期供体中快速生成多种治疗剂量的病毒特异性 T 细胞，用于潜在治疗 COVID-19 患者。
