The immunologic aspects of poxvirus oncolytic therapy

被引:28
|
作者
Worschech, Andrea [1 ,2 ,3 ,4 ]
Haddad, D. [1 ,4 ,5 ]
Stroncek, D. F. [6 ]
Wang, E. [2 ,3 ]
Marincola, Francesco M. [2 ,3 ]
Szalay, Aladar A. [1 ,4 ]
机构
[1] Genelux Corp, San Diego Sci Ctr, San Diego, CA 92109 USA
[2] NIH, CHI, Ctr Clin, Bethesda, MD 20892 USA
[3] NIH, IDIS, Dept Transfus Med, Bethesda, MD 20892 USA
[4] Univ Wurzburg, Inst Biochem, Virchow Ctr Expt Biomed, Wurzburg, Germany
[5] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA
[6] NIH, Cell Therapy Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA
关键词
Vaccinia virus; Oncolytic therapy; Innate immunity; Tumor rejection; NATURAL-KILLER-CELLS; VACCINIA-VIRUS; INTERFERON-GAMMA; IMMUNE-RESPONSE; INNATE IMMUNITY; T-CELLS; SPECIES-SPECIFICITY; ANTITUMOR IMMUNITY; CANCER-THERAPY; TUMOR-CELLS;
D O I
10.1007/s00262-009-0686-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The concept of using replicating oncolytic viruses in cancer therapy dates to the beginning of the twentieth century. However, in the last few years, an increasing number of pre-clinical and clinical trials have been carried out with promising preliminarily results. Novel, indeed, is the suggestion that viral oncolytic therapy might not operate exclusively through an oncolysis-mediated process but additionally requires the "assistance" of the host's immune system. Originally, the host's immune response was believed to play a predominant obstructive role against viral replication, hence limiting the anti-tumor efficacy of viral vectors. Recent data, however, suggest that the immune response may also play a key role in promoting tumor destruction in association with the oncolytic process. In fact, immune effector pathways activated during oncolytic virus-induced tumor rejection seem to follow a similar pattern to those observed when the broader phenomenon of immune-mediated tissue-specific rejection occurs in other immune-related pathologies. We recently formulated the "Immunologic Constant of Rejection" hypothesis, emphasizing commonalties in transcriptional patterns observed when tissue-destruction occurs: whether with a favorable outcome, such as in tumor rejection and pathogen clearance; or a destructive one, such as in allograft rejection or autoimmunity. Here, we propose that a similar mechanism induces clearance of virally infected tumors and that such a mechanism is primarily dependent on innate immune functions.
引用
收藏
页码:1355 / 1362
页数:8
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