新型溶瘤病毒:LCMV
  • 沙粒病毒淋巴细胞脉络丛脑膜炎病毒(LCMV)和临床上使用的Junin病毒疫苗(Candid#1)在多种肿瘤细胞中优先复制;
  • 病毒复制导致局部免疫活性延长,局部和远处转移肿瘤快速消退,疾病长期控制;
  • LCMV诱导抗肿瘤免疫,依赖于产生干扰素Ly6C(+)的单核细胞的募集,进一步增加肿瘤特异性CD8(+) T细胞;
  • 与其他溶瘤病毒和PD-1阻断剂不同,LCMV抗肿瘤疗效可观,给予治疗量的沙粒病毒,在肿瘤细胞内复制,通过促进局部免疫应答,而诱导肿瘤消退。
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Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

沙粒病毒时空限制性复制,诱导免疫监视和I型干扰素依赖性肿瘤缩小

10.1038/ncomms14447

2017-03-01, Article

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Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C(+) monocytes and additionally enhances tumour-specific CD8(+) T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses.

First Authors:
Halime Kalkavan

Correspondence Authors:
Martin Schuler,Karl S Lang

All Authors:
Halime Kalkavan,Piyush Sharma,Stefan Kasper,Iris Helfrich,Aleksandra A Pandyra,Asmae Gassa,Isabel Virchow,Lukas Flatz,Tim Brandenburg,Sukumar Namineni,Mathias Heikenwalder,Bastian Höchst,Percy A Knolle,Guido Wollmann,Dorothee von Laer,Ingo Drexler,Jessica Rathbun,Paula M Cannon,Stefanie Scheu,Jens Bauer,Jagat Chauhan,Dieter Häussinger,Gerald Willimsky,Max Löhning,Dirk Schadendorf,Sven Brandau,Martin Schuler,Philipp A Lang,Karl S Lang

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