McLaughlin Lauren P, Gottschalk Stephen, Rooney Cliona M, Bollard Catherine M
Department of Hematology/Oncology, Children's National Medical Center, 111 Michigan Ave., Washington, DC, 20010, USA.
The George Washington University, Washington, DC, USA.
Methods Mol Biol. 2017;1532:255-265. doi: 10.1007/978-1-4939-6655-4_19.
Epstein Barr virus (EBV) is a human gamma herpes virus that establishes latency in B cells after primary infection. EBV generally only causes a mild, self-limiting viral illness but is also associated with several malignancies including posttransplantation lymphoproliferative disorder in the immunosuppressed host as well as Hodgkin and non-Hodgkin lymphoma in the immune competent host. The expression of EBV antigens by lymphoma has important applications as targets for adoptive T cell therapy. However, as many lymphomas only express subdominant EBV antigens that are less immunogenic, novel strategies are needed to manufacture EBV-specific T cell products specific for Latent Membrane Protein 1 (LMP1) and LMP2, which are expressed in lymphomas with type II and III latency. While several techniques for manufacturing EBV-CTLs are described in the literature, this chapter focuses on one method for generating Good Manufacturing Practice (GMP)-compliant EBV-specific T cell products that are enriched with LMP1 and LMP2.
爱泼斯坦-巴尔病毒(EBV)是一种人类γ疱疹病毒,初次感染后可在B细胞中建立潜伏感染。EBV通常仅引起轻微的自限性病毒疾病,但也与多种恶性肿瘤有关,包括免疫抑制宿主中的移植后淋巴细胞增生性疾病以及免疫功能正常宿主中的霍奇金淋巴瘤和非霍奇金淋巴瘤。淋巴瘤中EBV抗原的表达作为过继性T细胞治疗的靶点具有重要应用。然而,由于许多淋巴瘤仅表达免疫原性较低的次要EBV抗原,因此需要新的策略来制备针对潜伏膜蛋白1(LMP1)和LMP2的EBV特异性T细胞产品,这两种蛋白在具有II型和III型潜伏感染的淋巴瘤中表达。虽然文献中描述了几种制备EBV特异性细胞毒性T淋巴细胞(EBV-CTL)的技术,但本章重点介绍一种制备符合药品生产质量管理规范(GMP)的富含LMP1和LMP2的EBV特异性T细胞产品的方法。