Systemic administration of platelets incorporating inactivated Sendai virus eradicates melanoma in mice.
Systemic administration of platelets incorporating inactivated Sendai virus eradicates melanoma in mice.
复制标题
全身注射掺有灭活仙台病毒的血小板可根除小鼠黑色素瘤。
DOI：
10.1038/mt.2014.128
复制
发表时间：
2014
影响因子：
12.4
通讯作者：
Y.
中科院分区：
文献类型：
--
作者：
Nishikawa;T.;Tung;L. Y. and Kaneda;Y.
肿瘤微环境包括由于癌细胞侵入血管引起的微出血而产生的许多纤维蛋白凝块，这表明血小板载体在全身癌症治疗中具有潜在的用途。我们先前报道了灭活仙台病毒（日本血凝病毒; HVJ）包膜（HVJ-E）激活抗肿瘤免疫并诱导癌细胞选择性凋亡。阻断HVJ-E全身给药的血凝活性通过掺入血小板而显著减弱。然后将掺入HVJ-E（PH复合物）的血小板注射到携带B16 F10黑素瘤的小鼠的尾静脉中。PH复合物主要积聚在肿瘤组织中，并引起各种免疫细胞在肿瘤床中的显著积聚。向荷黑色素瘤小鼠注射PH复合物显著减小了肿瘤大小，并且肿瘤生长最终被抑制。分泌的趋化因子调节后激活正常T表达和推测分泌（RANTES）上调后PH刺激。RANTES耗竭黑色素瘤荷瘤小鼠的细胞毒性T淋巴细胞活性显着衰减，并导致显着废除小鼠黑色素瘤抑制诱导的PH复合物。因此，血小板载体纳入病毒颗粒，特洛伊木马的癌症治疗，将提供一个新的方法，癌症治疗使用溶瘤病毒。
Tumor microenvironments include a number of fibrin clots due to the microbleeding caused by cancer cell invasion into blood vessels, which suggests the potential utility of a platelet vector for systemic cancer treatment. We previously reported that inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) activates anti-tumor immunity and induces cancer cell-selective apoptosis. The hemagglutination activity that blocks the systemic administration of HVJ-E was dramatically attenuated by incorporation into platelets. Platelets incorporating HVJ-E (PH complex) were then injected into the tail veins of B16F10 melanoma-bearing mice. The PH complex primarily accumulated in tumor tissues and caused the significant accumulation of various immune cells in the tumor bed. Injections of the PH complex to the melanoma-bearing mouse significantly reduced the tumor size, and the tumor growth was ultimately arrested. Secretion of the chemokine regulated upon activation normal T-expressed and presumably secreted (RANTES) was upregulated following PH stimulation. The RANTES-depletion in melanoma-bearing mice significantly attenuated the cytotoxic T lymphocyte activity and led to a dramatic abrogation of the mouse melanoma suppression induced by the PH complex. Thus, a platelet vector incorporating viral particles, a Trojan horse for cancer treatment, will provide a new approach for cancer therapy using oncolytic viruses.