Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration
Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration
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DOI：
10.1016/s0304-3835(01)00617-6
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发表时间：
2001-10-22
期刊：
影响因子：
9.7
通讯作者：
Walter, RJ
中科院分区：
文献类型：
--
作者：
Phuangsab, A;Lorence, RM;Walter, RJ
先前我们发现，单次局部注射禽副粘病毒新城疫病毒（NDV） 73-T株，可使胸腺小鼠的人类神经母细胞瘤和纤维肉瘤移植瘤长期完全消退。在这里，我们报告了NDV通过肿瘤内（IT）途径治疗多种人类肿瘤异种移植物或通过全身（腹腔，IP）途径治疗神经母细胞瘤异种移植物（6.5- 12mm直径）的抗肿瘤作用。对于IT治疗，小鼠被随机分为治疗组，并给予单次IT注射NDV 73-T，载药（磷酸盐缓冲盐水，PBS）或紫外线灭活NDV。对于全身治疗，皮下移植了IMR-32人神经母细胞瘤的小鼠（n = 18）接受了NDV （5 × 10(9) PFU）的IP注射。NDV对表皮样癌（KB8-5-11）、结肠癌（SW620和HT29）、大细胞肺（NCIH460）、乳腺癌（SKBR3）、前列腺癌（PO）和低传代结肠癌（MM17387）的肿瘤生长有显著抑制（77-96%）。在所有病例中，肿瘤用PBS或无复制能力、紫外线灭活的NDV治疗IT，显示肿瘤快速生长。单次IP注射NDV后，12只小鼠中有9只观察到IMR-32神经母细胞瘤完全消退，随访3-9个月无复发。6只神经母细胞瘤复发的小鼠在一次IP注射后接受了一到三次额外的NDV IP治疗。这6只小鼠中有3只表现出完全退化，没有复发。这些数据表明：(1)NDV给药无论是IT还是IP在该系统中都是一种有效的抗肿瘤治疗方法，(2)复制能力是达到最大效果所必需的，(3)多次NDV剂量比单次剂量更有效。这些研究为NDV作为溶瘤剂的临床前研究提供了进一步的理论依据。(C) 2001爱思唯尔科学爱尔兰有限公司版权所有。
Previously we showed that a single local injection of the avian paramyxovirus Newcastle disease virus (NDV) strain 73-T caused long-lasting, complete tumor regression of human neuroblastoma and fibrosarcoma xenografts in athymic mice. Here we report the antitumor effects of NDV administered by either the intratumoral (IT) route to treat a variety of human carcinoma xenografts or by the systemic (intraperitoneal, IP) route to treat neuroblastoma xenografts (6.5-12 mm in diameter). For IT treatments, mice were randomized into treatment groups and given a single IT injection of NDV 73-T, vehicle (phosphate buffered saline, PBS), or UV-inactivated NDV. For systemic therapy, mice (n = 18) with subcutaneous IMR-32 human neuroblastoma xenografts received IP injections of NDV (5 X 10(9) PFU). Significant tumor growth inhibition (77-96%) was seen for epidermoid (KB8-5-11), colon (SW620 and HT29), large cell lung (NCIH460), breast (SKBR3), prostate (PO), and low passage colon (MM17387) carcinoma xenografts treated IT with NDV. In all cases, tumors treated IT with PBS or replication-incompetent, UV-inactivated NDV displayed rapid tumor growth. After a single IP injection of NDV, complete regression of IMR-32 neuroblastomas was observed in 9 of 12 mice without recurrence for the 3-9 month follow-up period. Six mice with recurrent neuroblastomas after one IP injection received one to three additional IP treatments with NDV. Three of these six mice showed complete regression without recurrence. These data show that: (1) NDV administered either IT or IP is an effective antitumor therapy in this system, (2) replication competency is necessary for maximal effect, and (3) multiple NDV doses can be more effective than a single dose. These studies provide further rationale for the preclinical study of NDV as an oncolytic agent. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.