Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer.
Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer.
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DOI：
10.1158/0008-5472.can-14-2533
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发表时间：
2015-01-01
期刊：
影响因子：
11.2
通讯作者：
Hartmann LC
中科院分区：
文献类型：
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作者：
Galanis E;Atherton PJ;Maurer MJ;Knutson KL;Dowdy SC;Cliby WA;Haluska P Jr;Long HJ;Oberg A;Aderca I;Block MS;Bakkum-Gamez J;Federspiel MJ;Russell SJ;Kalli KR;Keeney G;Peng KW;Hartmann LC
麻疹病毒（MV）的Edmonston疫苗株在卵巢癌小鼠异种移植模型中具有显著的抗肿瘤活性。MV基因工程表达的钠碘转运体基因（MV-NIS）有助于定位病毒基因的表达，并提供了一个工具，肿瘤放射病毒治疗。在这里，我们报告了MV-NIS在紫杉醇和铂类耐药卵巢癌患者中的临床评价结果。MV-NIS每4周腹腔注射一次，最多6个周期。在这些接受过大量预治疗的卵巢癌患者中，治疗耐受性良好，且中位总生存期有希望;在16例接受高剂量水平（108-109 TCID 50）治疗的患者中未观察到剂量限制性毒性，其中位总生存期为26.5个月，与其他当代系列相比更为有利。MV受体CD 46和nectin-4表达通过免疫组织化学证实在患者肿瘤中。通过SPECT/CT上的123 I摄取证实了3例患者治疗后肿瘤中的钠碘转运体表达，并且与长期无进展生存期相关。治疗后的免疫监测显示识别肿瘤抗原IGFBP 2和FRα的效应T细胞增加，表明MV-NIS治疗引发了针对患者肿瘤的细胞免疫，并表明免疫机制介导了观察到的抗肿瘤作用。我们的研究结果支持MV-NIS作为一种有效的免疫病毒疗法的进一步临床评价。
Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up to 6 cycles. Treatment was well tolerated and associated with promising median overall survival in these patients with heavily pretreated ovarian cancer; no dose-limiting toxicity was observed in 16 patients treated at high-dose levels (108–109 TCID50), and their median overall survival of 26.5 months compared favorably with other contemporary series. MV receptor CD46 and nectin-4 expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in three patients by 123I uptake on SPECT/CTs and was associated with long progression-free survival. Immune monitoring posttreatment showed an increase in effector T cells recognizing the tumor antigens IGFBP2 and FRα, indicating that MV-NIS treatment triggered cellular immunity against the patients' tumor and suggesting that an immune mechanism mediating the observed antitumor effect. Our findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy.