Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses
Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses
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DOI：
10.1002/jgm.877
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发表时间：
2006-05-01
影响因子：
3.5
通讯作者：
Fong, Yuman
中科院分区：
文献类型：
--
作者：
Adusumilli, Prasad S.;Stiles, Brendon M.;Fong, Yuman
背景：恶性胸膜间皮瘤(MPM)是一种侵袭性癌症，目前的治疗方法难以奏效。用于基因治疗的溶瘤单纯疱疹病毒(HSV)是一种基因工程的复制能力强的病毒，它选择性地针对肿瘤细胞，而不影响正常的宿主组织。MPM的局部性、潜在的可及性和相对缺乏远处转移的特性使其特别适合于溶瘤病毒的治疗。方法：检测3株溶瘤HSV：6207、NV1020和NV1066对11种病理类型的MPM细胞的感染性、选择性复制、媒介传播和细胞毒力，包括对放射治疗、吉西他滨和顺铂耐药的细胞株。结果：3种溶瘤单纯疱疹病毒对所有受试的MPM细胞株均有较强的抑制作用。即使在很低浓度的MOI0.01(MOI：病毒感染的多样性，每个癌细胞的病毒颗粒比率)下，HSV对辐射、吉西他滨和顺铂耐药的MPM细胞也具有很高的疗效。NV1066是一种表达绿色荧光蛋白(GFP)的溶瘤单纯疱疹病毒，由于GFP在肿瘤细胞中的选择性感染和表达，NV1066能够在MPM小鼠模型中描述疾病的程度。NV1066能够减轻肿瘤负担，延长生存期，即使在疾病的晚期。结论：这些发现支持继续研究溶瘤HSV作为治疗耐药MPM患者的潜在治疗方法。版权所有(C)2006 John Wiley&Sons，Ltd.
Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy.Methods: The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: 6207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model.Results: All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. NV1066 was able to reduce the tumor burden and prolong Furthermore, survival even when treatment was at an advanced stage of the disease.Conclusion: These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM. Copyright (c) 2006 John Wiley & Sons, Ltd.