文章：

H-1细小病毒诱导的皮肤T细胞淋巴瘤新型异型球体模型中的溶瘤作用及肿瘤微环境免疫调节

H-1 Parvovirus-Induced Oncolysis and Tumor Microenvironment Immune Modulation in a Novel Heterotypic Spheroid Model of Cutaneous T-Cell Lymphoma

原文发布日期：30 July 2024

DOI: 10.3390/cancers16152711

类型: Article

开放获取: 是

英文摘要：

The rat protoparvovirus H-1 (H-1PV) is an oncolytic virus known for its anticancer properties in laboratory models of various human tumors, including non-Hodgkin lymphomas (NHL) of B-cell origin. However, H-1PV therapeutic potential against hematological malignancies of T-cell origin remains underexplored. The aim of the present study was to conduct a pilot preclinical investigation of H-1PV-mediated oncolytic effects in cutaneous T-cell lymphoma (CTCL), a type of NHL that is urgently calling for innovative therapies. We demonstrated H-1PV productive infection and induction of oncolysis in both classically grown CTCL suspension cultures and in a novel, in vivo-relevant, heterotypic spheroid model, but not in healthy donor controls, including peripheral blood mononuclear cells (PBMCs). H-1PV-mediated oncolysis of CTCL cells was not prevented by Bcl-2 overexpression and was accompanied by increased extracellular ATP release. In CTCL spheroid co-cultures with PBMCs, increased spheroid infiltration with immune cells was detected upon co-culture treatment with the virus. In conclusion, our preclinical data show that H-1PV may hold significant potential as an ingenious viroimmunotherapeutic drug candidate against CTCL.

摘要翻译： 

大鼠原细小病毒H-1（H-1PV）是一种溶瘤病毒，在包括B细胞起源的非霍奇金淋巴瘤（NHL）在内的多种人类肿瘤实验室模型中显示出抗癌特性。然而，H-1PV对T细胞起源的血液系统恶性肿瘤的治疗潜力尚未得到充分探索。本研究旨在对H-1PV在皮肤T细胞淋巴瘤（CTCL）中的溶瘤效应进行初步临床前研究，该疾病作为非霍奇金淋巴瘤的一种亚型，亟需创新疗法。我们证实H-1PV能在经典培养的CTCL悬浮细胞模型及新型体内相关异型球体模型中实现有效感染并诱导溶瘤效应，但在健康供体对照组（包括外周血单个核细胞）中未观察到该现象。Bcl-2过表达未能阻止H-1PV介导的CTCL细胞溶瘤作用，且该过程伴随细胞外ATP释放增加。在CTCL球体与PBMCs的共培养体系中，病毒处理后的共培养组检测到免疫细胞对球体的浸润增强。综上所述，我们的临床前数据表明，H-1PV作为针对CTCL的创新型病毒免疫治疗候选药物具有重要潜力。

原文链接：

H-1 Parvovirus-Induced Oncolysis and Tumor Microenvironment Immune Modulation in a Novel Heterotypic Spheroid Model of Cutaneous T-Cell Lymphoma