Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter
Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter
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DOI：
10.1158/1078-0432.ccr-05-1803
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发表时间：
2006-03-15
影响因子：
11.5
通讯作者：
Peng, KW
中科院分区：
文献类型：
--
作者：
Hasegawa, K;Pham, L;Peng, KW
目的：MV-CEA是一种溶瘤麻疹病毒，目前正在卵巢癌患者中进行检测，可通过检测血液中癌胚抗原(CEA)水平来监测其传播情况。MV-NIS是一种溶瘤麻疹病毒，编码甲状腺钠碘转运体(NIS)，其传播可以通过连续的放射性碘成像来定位。从单个病毒中同时表达CEA和NIS基因将结合敏感的定量表达监测(CEA)和放射性同位素表达图谱(NIS)。由于同时表达CEA和NIS的麻疹病毒复制动力学不佳，我们探索了MV-CEA和MV-NIS联合用于卵巢癌综合病毒治疗监测的可行性。SKOV3ip.1卵巢癌移植瘤仅接受MV-CEA、MV-NIS或MV-CEA+MV-NIS的联合治疗，通过检测血液CEA水平监测病毒基因表达，通过伽马相机成像监测病毒感染细胞的位置。令人惊讶的是，接受MV-CEA和MV-NIS联合治疗的小鼠对治疗的反应非常好，但这与血浆CEA水平比单独接受MV-CEA治疗的小鼠低10倍有关。体外研究表明，MV-NIS的复制动力学优于MV-CEA。结论：MV-CEA和MV-NIS联合治疗优于单独使用任何一种病毒，并可通过可溶性标志物多肽和伽马摄像对病毒治疗进行无创性监测。这对溶瘤麻疹病毒的临床发展具有重要意义。
Purpose: MV-CEA is an oncolytic measles virus currently being tested in patients with ovarian cancer and whose propagation can be monitored by measuring blood carcinoembryonic antigen (CEA) levels. MV-NIS is an oncolytic measles virus coding for the thyroidal sodium iodide symporter (NIS) whose propagation can be mapped by serial radioiodine imaging. Expression of both CEA and NIS genes from a single virus would combine sensitive, quantitative expression monitoring (CEA) with radioisotopic expression mapping (NIS). Because of the unfavorable replication kinetics of measles viruses expressing both CEA and NIS, we explored the feasibility of combining MV-CEA with MV-NIS for comprehensive virotherapy monitoring in ovarian cancer.Experimental Design and Results: Mice implanted with i.p. SKOV3ip.1 ovarian cancer xenografts received MV-CEA alone, MV-NIS alone, or a combination of MV-CEA plus MV-NIS.Viral gene expression was monitored by measuring blood CEA levels, and the location of virus-infected cells was monitored by gamma camera imaging. Surprisingly, mice receiving the combination of MV-CEA plus MV-NIS showed greatly superior responses to therapy, but this was associated with 10-fold lower plasma levels of CEA compared with mice treated with MV-CEA alone. In vitro studies showed superior replication kinetics of MV-NIS relative to MV-CEA. The gamma camera scans were considerably less sensitive than the plasma CEA marker for monitoring virus infection.Conclusions: Dual therapy with MV-CEA and MV-NIS is superior to treatment with either virus alone, and it allows noninvasive monitoring of virotherapy via soluble marker peptide and gamma camera imaging. This has important implications for the clinical development of oncolytic measles viruses.