Seng Michaela Su-Fern, Ng King Pan, Soh Teck Guan, Tan Thuan Tong, Chan Marieta, Maiwald Matthias, Tan Lip Kun, Linn Yeh Ching, Leung Wing
Department of Paediatric Hematology and Oncology, KK Women's and Children's Hospital, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore.
Department of Hematology, National University Hospital, Singapore, Singapore.
Cytotherapy. 2024 Oct;26(10):1170-1178. doi: 10.1016/j.jcyt.2024.05.014. Epub 2024 May 18.
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.
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.
A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m 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.
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.
移植后或血液系统癌症患者感染严重急性呼吸综合征（SARS）-CoV-2的原始毒株和早期变体后死亡风险更高。采用病毒特异性T细胞（VST）的过继性细胞疗法（ACT）可增强内源性T细胞免疫，以避免在病毒清除前病情恶化。
我们在2020年利用康复期和/或接种疫苗的供者建立了第三方SARS-CoV-2特异性T细胞（COVID-T）库（NCT04351659）。在一项I/II期研究（NCT04457726）中，2021年9月至2022年2月招募了13例SARS-CoV-2急性阳性且预计死亡风险高的成人和儿童患者。12例患者接受了至少1个HLA配型的单剂量COVID-T细胞。
75000或150000个IFN-γ+CD3+细胞/m SARS-CoV-2特异性T细胞的剂量均未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ACT后可检测到供者SARS-CoV-2特异性T细胞的8例患者中无人进展为重症疾病或死于COVID-19。相比之下，在其他4例无供者微嵌合体证据的患者中，2例死于COVID-19。
来自康复期或接种疫苗供者的长效第三方VST可快速制备，可能在未来大流行中具有临床应用价值，尤其是在全球实施疫苗接种之前。
