QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia Queensland, Australia.
PLoS Pathog. 2022 Feb 14;18(2):e1010339. doi: 10.1371/journal.ppat.1010339. eCollection 2022 Feb.
Adoptive T-cell immunotherapy has provided promising results in the treatment of viral complications in humans, particularly in the context of immunocompromised patients who have exhausted all other clinical options. The capacity to expand T cells from healthy immune individuals is providing a new approach to anti-viral immunotherapy, offering rapid off-the-shelf treatment with tailor-made human leukocyte antigen (HLA)-matched T cells. While most of this research has focused on the treatment of latent viral infections, emerging evidence that SARS-CoV-2-specific T cells play an important role in protection against COVID-19 suggests that the transfer of HLA-matched allogeneic off-the-shelf virus-specific T cells could provide a treatment option for patients with active COVID-19 or at risk of developing COVID-19. We initially screened 60 convalescent individuals and based on HLA typing and T-cell response profile, 12 individuals were selected for the development of a SARS-CoV-2-specific T-cell bank. We demonstrate that these T cells are specific for up to four SARS-CoV-2 antigens presented by a broad range of both HLA class I and class II alleles. These T cells show consistent functional and phenotypic properties, display cytotoxic potential against HLA-matched targets and can recognize HLA-matched cells infected with different SARS-CoV-2 variants. These observations demonstrate a robust approach for the production of SARS-CoV-2-specific T cells and provide the impetus for the development of a T-cell repository for clinical assessment.
过继性 T 细胞免疫疗法在治疗人类病毒并发症方面取得了令人鼓舞的成果，特别是在免疫功能低下且已用尽所有其他临床选择的患者中。从健康免疫个体中扩增 T 细胞为抗病毒免疫疗法提供了一种新方法，提供了快速的现货治疗方法，使用定制的人类白细胞抗原（HLA）匹配的 T 细胞。虽然这项研究的大部分重点是治疗潜伏性病毒感染，但越来越多的证据表明，SARS-CoV-2 特异性 T 细胞在预防 COVID-19 方面发挥着重要作用，这表明转移 HLA 匹配的同种异体现成病毒特异性 T 细胞可能为患有 COVID-19 或有发展为 COVID-19 风险的患者提供一种治疗选择。我们最初筛选了 60 名康复个体，并根据 HLA 分型和 T 细胞反应谱，选择了 12 名个体用于开发 SARS-CoV-2 特异性 T 细胞库。我们证明这些 T 细胞对广泛的 HLA Ⅰ类和Ⅱ类等位基因呈递的多达四种 SARS-CoV-2 抗原具有特异性。这些 T 细胞表现出一致的功能和表型特性，对 HLA 匹配的靶标具有细胞毒性潜力，并能识别感染不同 SARS-CoV-2 变体的 HLA 匹配细胞。这些观察结果证明了生产 SARS-CoV-2 特异性 T 细胞的可靠方法，并为开发用于临床评估的 T 细胞库提供了动力。
