Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program.
Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program.
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DOI：
10.1002/pbc.22535
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发表时间：
2010-08
影响因子：
3.2
通讯作者：
Smith, Malcolm A.
中科院分区：
文献类型：
--
作者：
Morton, Christopher L.;Houghton, Peter J.;Kolb, E. Anders;Gorlick, Richard;Reynolds, C. Patrick;Kang, Min H.;Maris, John M.;Keir, Stephen T.;Wu, Jianrong;Smith, Malcolm A.
Seneca Valley病毒（NTX-010）是一种非重组、可复制的RNA病毒，正在成人中进行1期临床试验，用于治疗具有神经内分泌特征的肿瘤。在此，我们评价了全身给予NTX-010的抗肿瘤活性。在1 × 10 − 4至104个病毒颗粒（vp）/细胞的条件下，对23种细胞系暴露96小时进行了体外NTX-010检测。体内NTX-010以3 × 1012 vp/kg静脉给药一次。使用了三种抗肿瘤活性指标：1）在临床环境后建模的客观缓解指标; 2）治疗与对照（T/C）肿瘤体积指标;和3）至事件时间（实体瘤模型的肿瘤体积增加4倍），基于每种异种移植物的治疗和对照动物的中位无事件生存期（EFS）进行测量。在体外，NTX-010在来自神经母细胞瘤、尤文肉瘤和横纹肌肉瘤组的细胞系亚组中显示出显著的细胞毒性作用。在体内，横纹肌肉瘤和神经母细胞瘤组观察到最一致的活性，所有4个腺泡状横纹肌肉瘤异种移植物和4/5个神经母细胞瘤异种移植物均达到CR或维持CR。在横纹肌样瘤、肾母细胞瘤和胶质母细胞瘤组中也观察到客观缓解。NTX-010在体外和体内均表现出高水平的活性。对现有测试和分子表征数据的进一步分析可能有助于定义与对NTX-010的反应相关的癌细胞的生物学特征。
Seneca Valley virus (NTX-010) is a non-recombinant, replication competent RNA virus that is undergoing phase 1 clinical trials in adults for tumors with neuroendocrine characteristics. Here we have evaluated the antitumor activity of NTX-010 administered systemically. In vitro NTX-010 was tested against 23 cell lines exposed for 96 hours at 1 × 10−4 to 104 viral particles (vp)/cell. In vivo NTX-010 was administered intravenously once at 3 × 1012 vp/kg. Three measures of antitumor activity were used: 1) an objective response measure modeled after the clinical setting; 2) a treated to control (T/C) tumor volume measure; and 3) a time to event (4-fold increase in tumor volume for solid tumor models), measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. In vitro NTX-010 demonstrated a marked cytotoxic effect in a subset of the cell lines from the neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma panels. In vivo the most consistent activity was observed for the rhabdomyosarcoma and the neuroblastoma panels, with all four of the alveolar rhabdomyosarcoma xenografts and 4 of 5 neuroblastoma xenografts achieving CR or maintained CR. Objective responses were also observed in the rhabdoid tumor, Wilms tumor, and glioblastoma panels. NTX-010 demonstrated a high level of activity both in vitro and in vivo. Further analysis of existing testing and molecular characterization data may help define the biological characteristics of cancer cells that are associated with response to NTX-010.
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影响因子：
9.7
作者：
Phuangsab, A;Lorence, RM;Walter, RJ
通讯作者：
Walter, RJ
DOI：
10.1158/1078-0432.ccr-07-5090
发表时间：
2008-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Neale G;Su X;Morton CL;Phelps D;Gorlick R;Lock RB;Reynolds CP;Maris JM;Friedman HS;Dome J;Khoury J;Triche TJ;Seeger RC;Gilbertson R;Khan J;Smith MA;Houghton PJ
通讯作者：
Houghton PJ
影响因子：
5.7
作者：
Frgala, Tomas;Kalous, Ondrej;Reynolds, C. Patrick
通讯作者：
Reynolds, C. Patrick
影响因子：
11.5
作者：
Graham, C;Tucker, C;Houghton, PJ
通讯作者：
Houghton, PJ
影响因子：
7.3
作者：
Lae, M.;Ahn, E. H.;Ladanyi, M.
通讯作者：
Ladanyi, M.