Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
Cell Therapy Unit, Department of Regenerative Medicine, Ghent University Hospital, Ghent, Belgium.
Acta Clin Belg. 2021 Dec;76(6):482-486. doi: 10.1080/17843286.2020.1752446. Epub 2020 Apr 14.
Cytomegalovirus (CMV) infection is one of the most common complications in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. The classic antiviral treatments have shown clinical efficacy but are often associated with drug resistance. Reconstitution of CMV-specific cellular immunity is essential in controlling CMV infection; therefore, adoptive transfer of CMV-specific T cells is a promising treatment option. We treated a patient with a multidrug resistant CMV infection after haploidentical HSCT with CMV-specific T cells. The T cells were derived from the HSCT donor who was CMV seropositive. We generated the T cells by a short-term Good Manufacturing Practice (GMP) grade protocol in which a leukapheresis product of the HSCT donor was stimulated with the immunodominant antigen pp65 and interferon-γ secreting cells were isolated. A total of 5 × 10 T cells were administered to the patient within 30 hours after leukapheresis. The patient was closely monitored for reconstitution of antiviral T cell immunity and viral replication after adoptive T cell transfer. We observed an in vivo expansion of both CD4 and CD8 CMV-specific T cells associated with a significant decrease in viral burden and clinical improvement. This case report further supports the feasibility and effectiveness of adoptive donor T cell transfer for the treatment of drug resistant CMV infections after allo-HSCT.
巨细胞病毒(CMV)感染是异基因造血干细胞移植(allo-HSCT)受者最常见的并发症之一。经典的抗病毒治疗已显示出临床疗效,但常伴有耐药性。重建 CMV 特异性细胞免疫对于控制 CMV 感染至关重要;因此,过继转移 CMV 特异性 T 细胞是一种很有前途的治疗选择。我们用 CMV 特异性 T 细胞治疗了一例 HLA 半相合 HSCT 后发生多药耐药性 CMV 感染的患者。T 细胞来源于 CMV 血清阳性的 HSCT 供者。我们通过短期的良好生产规范(GMP)级方案生成 T 细胞,该方案中,HSCT 供者的白细胞分离物用免疫优势抗原 pp65 刺激,并分离出干扰素-γ分泌细胞。在白细胞分离后 30 小时内,向患者输注了 5×10 T 细胞。在过继性 T 细胞转移后,我们密切监测患者抗病毒 T 细胞免疫重建和病毒复制情况。我们观察到 CD4 和 CD8 CMV 特异性 T 细胞的体内扩增与病毒载量的显著下降和临床改善相关。本病例报告进一步支持了过继性供者 T 细胞转移治疗 allo-HSCT 后耐药性 CMV 感染的可行性和有效性。