Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC.
Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC; Division of Allergy and Immunology, Children's National Hospital, Washington, DC; GW Cancer Center, George Washington University, Washington, DC.
Semin Hematol. 2023 Jan;60(1):10-19. doi: 10.1053/j.seminhematol.2022.12.002. Epub 2022 Dec 23.
Hematopoietic stem cell transplantation (HSCT) has been used as a curative standard of care for moderate to severe primary immunodeficiency disorders as well as relapsed hematologic malignancies for over 50 years [1,2]. However, chronic and refractory viral infections remain a leading cause of morbidity and mortality in the immune deficient period following HSCT, where use of available antiviral pharmacotherapies is limited by toxicity and emerging resistance [3]. Adoptive immunotherapy using virus-specific T cells (VSTs) has been explored for over 2 decades [4,5] in patients post-HSCT and has been shown prior phase I-II studies to be safe and effective for treatment or preventions of viral infections including cytomegalovirus, Epstein-Barr virus, BK virus, and adenovirus with minimal toxicity and low risk of graft vs host disease [6-9]. This review summarizes methodologies to generate VSTs the clinical results utilizing VST therapeutics and the challenges and future directions for the field.
造血干细胞移植(HSCT)作为一种治疗中重度原发性免疫缺陷疾病以及复发性血液系统恶性肿瘤的标准疗法已经应用了 50 多年[1,2]。然而,慢性和难治性病毒感染仍然是 HSCT 后免疫缺陷期发病率和死亡率的主要原因,现有的抗病毒药物治疗因毒性和耐药性而受到限制[3]。在 HSCT 后患者中,使用病毒特异性 T 细胞(VST)的过继免疫疗法已经探索了 20 多年[4,5],并在之前的 I-II 期研究中显示出针对包括巨细胞病毒、EB 病毒、BK 病毒和腺病毒在内的病毒感染的治疗或预防是安全有效的,且毒性最小,移植物抗宿主病的风险低[6-9]。本文综述了生成 VST 的方法、利用 VST 治疗的临床结果以及该领域的挑战和未来方向。