STABLE CLONE PRODUCTION FOR ANTI-EBV MONOCLONAL ANTIBODIES

EB病毒（Epstein-Barr virus，EBV）是干细胞和器官移植受者发生移植后淋巴组织增生性疾病（PTLD）和EBV淋巴瘤的主要原因。移植前EBV血清阴性的人比EBV血清阳性的人患PTLD的风险高10- 76倍。患有X连锁淋巴组织增生性疾病、严重联合免疫缺陷和某些其他免疫缺陷的人具有发生致命性EBV疾病（包括淋巴瘤）的高风险，伴有原发感染。因此，单克隆抗体输注到EBV血清阴性免疫功能低下的人可能会降低PTLD或EBV淋巴瘤的发病率。在小鼠移植模型（使用人源化小鼠）中，国家过敏和传染病研究所（NIAID）发现，给予小鼠两种单克隆抗体（mAb）中的任何一种，EBV mAb A10-V2-LS或EBV mAb B10-LS，可以保护动物免受EBV病毒血症和EBV淋巴瘤的侵害。 NCI癌症治疗和诊断部门与国家过敏和传染病研究所（NIAID）合作，要求产生抗Epstein-巴尔病毒（EBV）单克隆抗体的稳定克隆。本任务指令产生的稳定克隆的成功生产将支持未来的生产工艺开发和两种新型抗EBV抗体的cGMP生产，用于临床前和人类临床研究的评价。这些抗体靶向EBV gH/gL和EBV gp 42，并有效地中和EBV感染，阻断融合，并保护人源化小鼠免于死亡、病毒血症、EBV组织浸润和淋巴瘤。此外，这些抗体是迄今为止最有效的gH/gL mAb和gp 42 mAb，可用于预防移植受者或可能对EBV疫苗反应不佳的免疫功能低下个体的EBV感染或疾病。

Epstein-Barr virus (EBV) is the major cause of post-transplant lymphoproliferative disease (PTLD) and EBV lymphoma in stem cell and organ transplant recipients. Persons who are EBV seronegative before transplant have a 10- to 76-fold higher risk of developing PTLD than EBV seropositive persons. Persons with X-linked lymphoproliferative disease, severe combined immunodeficiency, and certain other immunodeficiencies are at high risk for developing fatal EBV disease, including lymphomas, with primary infection. Thus, infusion of monoclonal antibodies into EBV seronegative immunocompromised persons may reduce the incidence of PTLD or EBV lymphomas. In a mouse transplant model (using humanized mice), the National Institute of Allergy and Infectious Diseases (NIAID) found that giving the mice either of the two monoclonal antibodies (mAbs), EBV mAb A10-V2-LS or EBV mAb B10-LS, protected the animals from EBV viremia and EBV lymphomas. The Division of Cancer Treatment and Diagnosis, NCI in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) is requesting the generation of stable clones for anti-Epstein-Barr virus (EBV) monoclonal antibodies. Successful production of stable clones resulting from this Task Order will support future manufacturing process development and the cGMP production of two, novel anti-EBV antibodies for evaluation in preclinical and human clinical studies. These antibodies target EBV gH/gL and EBV gp42, and potently neutralize EBV infection, block fusion, and protect humanized mice from death, viremia, EBV tissue infiltration, and lymphoma. Additionally, these antibodies are the most potent gH/gL mAb and gp42 mAb to date and might be used to prevent EBV infection or disease in transplant recipients or in immunocompromised individuals who may not respond well to EBV vaccines.