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Rapid GMP-compliant expansion of SARS-CoV-2-specific T cells from convalescent donors for use as an allogeneic cell therapy for COVID-19
bioRxiv - Immunology Pub Date : 2020-08-05 , DOI: 10.1101/2020.08.05.237867
Rachel S Cooper , Alasdair R Fraser , Linda Smith , Paul Burgoyne , Stuart N Imlach , Lisa M Jarvis , Sharon Zahra , Marc L. Turner , John DM Campbell

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. Here we show that SARS-CoV-2-exposed blood donations contain CD4 and CD8 memory T cells specific for SARS-CoV-2 spike, nucleocapsid and membrane antigens. These peptides can be used to isolate virus-specific T cells in a GMP-compliant process. These T cells can be rapidly expanded using GMP-compliant reagents for use as a therapeutic product. 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 1010 to 1011 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 treatment of COVID-19 patients.

中文翻译:

恢复期供体的SARS-CoV-2特异性T细胞的快速GMP顺应性扩增,用作COVID-19的同种异体细胞疗法

由SARS-CoV-2病毒引起的COVID-19疾病的特征是效应T细胞失调和耗尽T细胞积聚。T细胞对病毒的反应可以通过使用供体来源的病毒特异性T细胞的过继细胞疗法来纠正。在这里,我们显示暴露于SARS-CoV-2的献血包含对SARS-CoV-2尖峰,核衣壳和膜抗原特异的CD4和CD8记忆T细胞。这些肽可用于在符合GMP的过程中分离病毒特异性T细胞。这些T细胞可以使用符合GMP的试剂快速扩增,用作治疗产品。记忆和效应表型存在于选定的病毒特异性T细胞中,但我们的方法迅速扩展了所需的中央记忆表型。在21天的培养过程中可获得1010至1011 T细胞的生产产量。从而,
更新日期:2020-08-06
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