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RhoC:转移性癌症治疗性疫苗接种的新靶点。

RhoC a new target for therapeutic vaccination against metastatic cancer.

作者信息

Wenandy Lynn, Sørensen Rikke Baek, Svane Inge Marie, Thor Straten Per, Andersen Mads Hald

机构信息

Center for Cancer Immune therapy (CCIT), Department of Hematology, Herlev University Hospital, 2730, Herlev, Denmark.

出版信息

Cancer Immunol Immunother. 2008 Dec;57(12):1871-8. doi: 10.1007/s00262-008-0517-2. Epub 2008 Apr 16.

Abstract

Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies.

摘要

大多数癌症死亡是由转移灶的形成所致。RhoC表达增加与多种癌症转移潜能增强有关。因此,RhoC蛋白是药物设计的一个有吸引力的靶点。癌症免疫疗法的临床应用在多个领域正迅速推进,包括抗肿瘤反应性T细胞的过继性转移和“治疗性”疫苗的使用。RhoC在癌症中的过表达以及该蛋白通过下调或表达缺失实现免疫逃逸会降低癌症发病率和死亡率这一事实,使得RhoC成为抗癌免疫疗法极具吸引力的靶点。在此,我们描述了一个来自RhoC的HLA - A3限制性表位,它可被细胞毒性T细胞识别。此外,RhoC特异性T细胞对不同来源的HLA匹配癌细胞显示出细胞毒性潜能。因此,RhoC可能成为抗癌免疫治疗策略的一个重要且广泛适用的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbc4/11030672/6aec3b4286ea/262_2008_517_Fig1_HTML.jpg

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