NEWCASTLE-DISEASE VIRUS AS AN ANTINEOPLASTIC AGENT - INDUCTION OF TUMOR NECROSIS FACTOR-ALPHA AND AUGMENTATION OF ITS CYTO-TOXICITY
NEWCASTLE-DISEASE VIRUS AS AN ANTINEOPLASTIC AGENT - INDUCTION OF TUMOR NECROSIS FACTOR-ALPHA AND AUGMENTATION OF ITS CYTO-TOXICITY
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DOI：
10.1093/jnci/80.16.1305
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发表时间：
1988-10-19
影响因子：
10.3
通讯作者：
KELLEY, KW
中科院分区：
文献类型：
--
作者：
LORENCE, RM;ROOD, PA;KELLEY, KW
新城疫病毒（NDV）溶瘤菌株73-T已被报道对癌症患者的治疗有益，但其作用机制尚不清楚。在这项研究中，NDV菌株73-T和NDV野生型分离株被发现是人外周血单个核细胞和大鼠脾细胞产生肿瘤坏死因子（TNF）的有效诱导剂。抗体抑制实验鉴定出TNF- α。作为NDV在pbmc中诱导的TNF的主要种类。重组人TNF- α的作用。（rHuTNF-. α）对人类癌细胞的作用。无论是rHuTNF -.alpha。ndvv刺激pbmc的上清液对tnf耐药的人类恶性黑色素瘤细胞系MEL-14也没有细胞毒性。然而，当用NDV菌株73-T处理MEL-14细胞时，rHuTNF-. α。ndv刺激pbmc的上清液分别杀死了48%和55%的肿瘤细胞。NDV治疗还使TNF对TNF耐药的人恶性黑色素瘤细胞系MEL-21和人骨髓性白血病细胞系K562具有易感性。与对ndvv治疗的癌细胞增强的细胞毒性相反，rHuTNF-. α。这些结果表明NDV抗肿瘤活性的两个重要机制：(a)诱导TNF-. α。(b)肿瘤细胞对TNF- α细胞溶解作用的敏感性增强。
The oncolytic strain 73-T of Newcastle disease virus (NDV) has been reported to be beneficial in the treatment of cancer patients, but little is known about its mechanism of action. In this study, NDV strain 73-T and a wild-type isolate of NDV were found to be potent inducers of tumor necrosis factor (TNF) production by both human peripheral blood mononuclear cells (PBMCs) and rat splenocytes. Antibody inhibition experiments identified TNF-.alpha. as the major species of TNF induced by NDV in PBMCs. The effect of recombinant human TNF-.alpha. (rHuTNF-.alpha.) on human cancer cells was then examined. Neither rHuTNF-.alpha. nor supernatants from NDV-stimulated PBMCs were cytotoxic toward the TNF-resistant human malignant melanoma cell line MEL-14. However, when MEL-14 cells were treated with NDV strain 73-T, both rHuTNF-.alpha. and supernatants from NDV-stimulated PBMCs killed 48% and 55%, respectively, of these tumor cells. Treatment with NDV also conferred TNF susceptibility to the TNF-resistant human malignant melanoma cell line MEL-21 and the human myelogenous leukemia cell line K562. In contrast to its enhanced cytotoxicity toward NDV-treated cancer cells, rHuTNF-.alpha. had no effect on NDV-treated normal human PBMCs proliferating in response to concanavalin A. These results suggest two important mechansims for the antineoplastic activity of NDV: (a) induction of TNF-.alpha. secretion by human PBMCs and (b) enhancement of the sensitivity of neoplastic cells to the cytolytic effects of TNF-.alpha.