Gärtner Kathrin, Luckner Manja, Wanner Gerhard, Zeidler Reinhard
Research Unit Gene Vectors, Helmholtz Centre Munich German Research Centre for Environmental Health, Munich, Germany.
Department of Biology I, Ludwig-Maximilians-Universität, Munich, Germany.
J Extracell Vesicles. 2019 Feb 11;8(1):1573051. doi: 10.1080/20013078.2019.1573051. eCollection 2019.
Extracellular vesicles (EVs) are important mediators of cell-cell communication. Intriguingly, EVs can be engineered and thus exploited for the targeted transfer of functional proteins of interest. Thus, engineered EVs may constitute attractive tools for the development of novel therapeutic interventions, like cancer immunotherapies, vaccinations or targeted drug delivery. Here, we describe a novel experimental immunotherapeutic approach for the adjuvant treatment of chronic lymphocytic leukaemia (CLL) based on engineered EVs carrying gp350, the major glycoprotein of Epstein-Barr virus (EBV), CD40L, a central immune accessory molecule and pp65, an immunodominant antigen of the human cytomegalovirus (CMV). We show that these engineered EVs specifically interact with malignant B cells from CLL patients and render these cells immunogenic to allogeneic and autologous EBV- and CMV-specific CD4+ and CD8+ T cells. Collectively, co-opting engineered EVs to re-target the strong herpesviral immunity in CLL patients to malignant cells constitutes an attractive strategy for the adjuvant treatment of a still incurable disease. : CLL: chronic lymphocytic leukaemia; EBV: Epstein-Barr virus; CMV: cytomegalovirus.
细胞外囊泡（EVs）是细胞间通讯的重要介质。有趣的是，EVs可以被改造，从而用于靶向递送感兴趣的功能蛋白。因此，工程化的EVs可能成为开发新型治疗干预措施（如癌症免疫疗法、疫苗接种或靶向药物递送）的有吸引力的工具。在此，我们描述了一种基于携带gp350（爱泼斯坦-巴尔病毒（EBV）的主要糖蛋白）、CD40L（一种核心免疫辅助分子）和pp65（人巨细胞病毒（CMV）的免疫显性抗原）的工程化EVs的新型实验性免疫治疗方法，用于慢性淋巴细胞白血病（CLL）的辅助治疗。我们表明，这些工程化的EVs与CLL患者的恶性B细胞特异性相互作用，并使这些细胞对同种异体和自体EBV及CMV特异性CD4+和CD8+ T细胞具有免疫原性。总的来说，利用工程化的EVs将CLL患者强大的疱疹病毒免疫力重新靶向恶性细胞，构成了一种治疗这种仍无法治愈疾病的有吸引力的辅助治疗策略。：CLL：慢性淋巴细胞白血病；EBV：爱泼斯坦-巴尔病毒；CMV：巨细胞病毒
