复制缺陷型腺病毒介导糖调节蛋白GRP94表达应用于肿瘤免疫基因治疗
摘要
研究背景：肿瘤细胞群为克隆性生长，包含大量的基因突变，因而每一种肿瘤均有其独特的抗原肽，具有潜在的引起肿瘤免疫反应的功能。一般情况下肿瘤细胞并不能引起足够的免疫反应，其中很重要的一个原因是因为抗原递呈细胞功能不足或不适。因此提高肿瘤抗原的递呈能力，有可能引起有效的抗肿瘤免疫反应。
糖调节蛋白94(GRP94)是热休克蛋白HSP90家族的一员，位于细胞内质网，其功能与蛋白质在内质网中的折叠与装配密切相关。在细胞经受压力的情况下(如热压力，糖缺乏等)，GRP94表达显著升高，结合并保护细胞蛋白不被降解，对蛋白质结构、功能有非常重要的作用。
近年来，由于GRP94可能在肿瘤免疫治疗中有重要作用而受到广泛注意。研究显示，在小鼠肿瘤模型中，肿瘤组织来源的GRP94可以刺激抗肿瘤免疫反应一它既能刺激天然免疫反应，也可引起适应性免疫反应。对其深入研究可能为肿
Background: It has been shown that tumor associated glucose-regulated protein 94 (GRP94/gp96), a HSP90 family member, elicits both innate and adaptive immune responses and shows great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the efficacy of many immunotherapies is often not ideal when used alone.
Adenoviruses have been characterized extensively since their initial description. Replication-deficient adenoviruses are attractive vectors for cancer gene therapy and adenoviruses-mediated gene therapy has been proposed as an alternative treatment for advanced cancers.
In this study, we explored the therapeutic efficacy of a combined adenovims mediated-GRP94 immunotherapy and radiation therapy strategy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model.
糖调节蛋白94(GRP94)是热休克蛋白HSP90家族的一员，位于细胞内质网，其功能与蛋白质在内质网中的折叠与装配密切相关。在细胞经受压力的情况下(如热压力，糖缺乏等)，GRP94表达显著升高，结合并保护细胞蛋白不被降解，对蛋白质结构、功能有非常重要的作用。
近年来，由于GRP94可能在肿瘤免疫治疗中有重要作用而受到广泛注意。研究显示，在小鼠肿瘤模型中，肿瘤组织来源的GRP94可以刺激抗肿瘤免疫反应一它既能刺激天然免疫反应，也可引起适应性免疫反应。对其深入研究可能为肿
Background: It has been shown that tumor associated glucose-regulated protein 94 (GRP94/gp96), a HSP90 family member, elicits both innate and adaptive immune responses and shows great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the efficacy of many immunotherapies is often not ideal when used alone.
Adenoviruses have been characterized extensively since their initial description. Replication-deficient adenoviruses are attractive vectors for cancer gene therapy and adenoviruses-mediated gene therapy has been proposed as an alternative treatment for advanced cancers.
In this study, we explored the therapeutic efficacy of a combined adenovims mediated-GRP94 immunotherapy and radiation therapy strategy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model.
引文
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