Abstract：
BACKGROUND: Post-transplant or hematological cancer patients have a higher risk of mortality after infection with ancestral and early variants of severe acute respiratory syndrome (SARS)-CoV-2. Adoptive cell therapy (ACT) with virus-specific T cells (VSTs) could augment endogenous T cell immunity to avoid disease deterioration before viral clearance.
METHODS: We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors. In a phase I/II study (NCT04457726), 13 adult and pediatric patients, acutely positive for SARS-CoV-2 and predicted to have a high chance of mortality, were recruited from September 2021 to February 2022. Twelve patients received a single dose of COVID-T cells, matched on at least 1 HLA.
RESULTS: A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m2 SARS-COV-2-specific T cells did not cause cytokine release syndrome, acute respiratory distress syndrome, or graft-versus-host disease. In the 8 patients who had detectable donor SARS-COV-2-specific T cells after ACT, none progressed to severe disease or died with COVID-19. In contrast, among the other four patients without evidence of donor micro-chimerism, two died of COVID-19.
CONCLUSIONS: Long-acting third-party VSTs from convalescent or vaccinated donors could be expediently produced and might be clinically useful in future pandemics, particularly before global vaccination is implemented.
METHODS: We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors. In a phase I/II study (NCT04457726), 13 adult and pediatric patients, acutely positive for SARS-CoV-2 and predicted to have a high chance of mortality, were recruited from September 2021 to February 2022. Twelve patients received a single dose of COVID-T cells, matched on at least 1 HLA.
RESULTS: A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m2 SARS-COV-2-specific T cells did not cause cytokine release syndrome, acute respiratory distress syndrome, or graft-versus-host disease. In the 8 patients who had detectable donor SARS-COV-2-specific T cells after ACT, none progressed to severe disease or died with COVID-19. In contrast, among the other four patients without evidence of donor micro-chimerism, two died of COVID-19.
CONCLUSIONS: Long-acting third-party VSTs from convalescent or vaccinated donors could be expediently produced and might be clinically useful in future pandemics, particularly before global vaccination is implemented.
摘要：
背景：移植后或血液系统癌症患者在感染严重急性呼吸道综合征（SARS）-CoV-2的祖先和早期变种后死亡的风险更高。使用病毒特异性T细胞（VST）的过继细胞疗法（ACT）可以增强内源性T细胞免疫力，以避免病毒清除前疾病恶化。
方法：我们于2020年使用康复期和/或接种疫苗的供体建立了第三方SARS-CoV-2特异性T细胞（COVID-T）库（NCT04351659）。在I/II期研究（NCT04457726）中，13名成人和儿童患者，SARS-CoV-2呈急性阳性，并预测有很高的死亡率，于2021年9月至2022年2月招募。12名患者接受了单剂量的COVID-T细胞，至少1个HLA匹配。
结果：剂量为75,000或150,000个IFN-γ+CD3+细胞/m2SARS-COV-2特异性T细胞不会引起细胞因子释放综合征，急性呼吸窘迫综合征,或移植物抗宿主病。在8例患者中，在ACT后有可检测到的供体SARS-COV-2特异性T细胞，无一例进展为严重疾病或死于COVID-19。相比之下,在其他四名没有供体微嵌合证据的患者中，两人死于COVID-19。
结论：可以方便地生产来自康复期或接种疫苗的供体的长效第三方VST，并可能在未来的大流行中具有临床用途，特别是在实施全球疫苗接种之前。
方法：我们于2020年使用康复期和/或接种疫苗的供体建立了第三方SARS-CoV-2特异性T细胞（COVID-T）库（NCT04351659）。在I/II期研究（NCT04457726）中，13名成人和儿童患者，SARS-CoV-2呈急性阳性，并预测有很高的死亡率，于2021年9月至2022年2月招募。12名患者接受了单剂量的COVID-T细胞，至少1个HLA匹配。
结果：剂量为75,000或150,000个IFN-γ+CD3+细胞/m2SARS-COV-2特异性T细胞不会引起细胞因子释放综合征，急性呼吸窘迫综合征,或移植物抗宿主病。在8例患者中，在ACT后有可检测到的供体SARS-COV-2特异性T细胞，无一例进展为严重疾病或死于COVID-19。相比之下,在其他四名没有供体微嵌合证据的患者中，两人死于COVID-19。
结论：可以方便地生产来自康复期或接种疫苗的供体的长效第三方VST，并可能在未来的大流行中具有临床用途，特别是在实施全球疫苗接种之前。
