Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner University Children's Hospital, Ludwig Maximilian University Munich, Lindwurmstrasse 4, 80337, Munich, Germany.
German Center for Infection Research (DZIF), Munich, Germany.
J Hematol Oncol. 2019 Feb 6;12(1):13. doi: 10.1186/s13045-019-0701-1.
Allogeneic hematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T -cell immunity in patients with refractory viral infections after allogeneic HSCT.
This narrative review summarizes clinical evidence and developments of almost 30 years of adoptive T -cell transfer. The review is based on evidence extracted from PubMed searches and the clinical and experimental work of the authors.
Viral infections after HSCT are frequently caused by the endogenous reactivation of persistent pathogens such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV). Current antiviral medication is not satisfactory and does not treat the underlying pathophysiology which is the lack of specific T -cell immunity. Adoptive transfer of virus-specific T cells could be a potentially curative, pathogen-specific, and non-toxic treatment providing long-term immunity against the virus. The isolation of virus-specific T cells from a healthy donor and infusion into a recipient is known as adoptive T -cell transfer and has been performed in many patients using different treatment protocols. Based on basic research, new isolation protocols aim at a safe and fast availability of cellular products for adoptive T -cell transfer. We summarize preclinical and clinical data on each of the main pathogens and on the technical approaches currently available to target either single antigens or even multiple pathogens.
Cellular therapy is considered as one of the major recent breakthroughs in medicine. Translation of this individualized treatment into first-line clinical routine is still limited. Main hurdles are availability of the technique, limited compatibility of classical phase III designs with cellular therapy, and regulatory restrictions. Multinational efforts are required to clarify the status of cellular treatment in first-line clinical routine with the overall objective to strengthen evidence-based treatment guidelines for the treatment of refractory viral infections post HSCT.
异基因造血干细胞移植（HSCT）可使患者短暂但明显地处于免疫抑制状态，在此期间，病毒感染是发病率和死亡率的重要原因。过继转移病毒特异性 T 细胞是一种很有吸引力的方法，可以在异基因 HSCT 后恢复对难治性病毒感染患者的保护性 T 细胞免疫。
本综述总结了近 30 年来过继性 T 细胞转移的临床证据和进展。该综述基于从 PubMed 搜索中提取的证据以及作者的临床和实验工作。
HSCT 后的病毒感染通常是由潜伏病原体（如巨细胞病毒（CMV）、EB 病毒（EBV）和腺病毒（AdV））的内源性再激活引起的。目前的抗病毒药物并不令人满意，也不能治疗潜在的病理生理学，即缺乏特异性 T 细胞免疫。过继转移病毒特异性 T 细胞可能是一种潜在的、有针对性的、无毒的治疗方法，可以提供针对病毒的长期免疫。从健康供体中分离病毒特异性 T 细胞并输注给受体的过程称为过继性 T 细胞转移，已经在许多患者中使用不同的治疗方案进行了。基于基础研究，新的分离方案旨在安全、快速地获得用于过继性 T 细胞转移的细胞产品。我们总结了关于每种主要病原体的临床前和临床数据，以及目前用于靶向单一抗原甚至多种病原体的技术方法。
细胞疗法被认为是医学的重大近期突破之一。将这种个体化治疗转化为一线临床常规仍然受到限制。主要障碍是技术的可用性、经典 III 期设计与细胞疗法的兼容性有限以及监管限制。需要跨国努力来澄清细胞治疗在一线临床常规中的地位，总体目标是加强基于证据的治疗指南，以治疗 HSCT 后的难治性病毒感染。
