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腺病毒-shRNA-SOCS1 病毒增强 HPV16 E7 肽脉冲树突状细胞疫苗的免疫治疗效果

Enhanced immunotherapeutic effect of modified HPV16 E7-pulsed dendritic cell vaccine by an adeno-shRNA-SOCS1 virus.

机构信息

School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.

出版信息

Int J Oncol. 2013 Oct;43(4):1151-9. doi: 10.3892/ijo.2013.2027. Epub 2013 Jul 22.

Abstract

Cervical cancer is the second most common cause of cancer-related deaths among women worldwide. However, no efficient therapy exists against cervical cancer and current treatments have several disadvantages. One possible novel approach is to develop immune-based strategies using tumor antigen-loaded dendritic cells (DCs) for the induction of cellular antitumor immunity. In this study, we created a modified HPV16 E7, HPV16mE7, to reduce its transformation activity and to enhance its antigenicity. The siRNA delivery technique was used to silence the suppressor of cytokine signaling 1 (SOCS1) gene in DCs. BM-derived DCs infected by ad-shRNA-SOCS1 were pulsed with the HPV16mE7 protein and then were transfused into mouse models bearing TC-1 tumor cells expressing HPV16 E6/E7. IFN-γ, cytokine (TNF-α, IL-12, IL-6) expression, anti-E7 antibody and cytotoxic T lymphocyte (CTL) levels were measured. The survival rate, survival days and the tumor volume of the mouse models from the different treatment groups were monitored. The data showed that the mE7-pulsed DC vaccine enhanced by adenovirus-mediated SOCS1 silencing exhibited better immunotherapeutic effect on the allografted tumor mouse models. The method by silencing SOCS1 in HPV16mE7 protein-pulsed DCs may provide a new strategy for the development of safe and effective immunotherapy for cervical cancer.

摘要

宫颈癌是全球女性癌症相关死亡的第二大主要原因。然而,目前针对宫颈癌还没有有效的治疗方法,而且现有的治疗方法存在许多缺点。一种可能的新方法是开发基于免疫的策略,使用负载肿瘤抗原的树突状细胞(DC)来诱导细胞抗肿瘤免疫。在这项研究中,我们构建了一种改良的 HPV16 E7(HPV16mE7),以降低其转化活性并增强其抗原性。使用 siRNA 递送技术沉默 DC 中的细胞因子信号转导抑制因子 1(SOCS1)基因。用 ad-shRNA-SOCS1 感染的 BM 来源的 DC 被 HPV16mE7 蛋白脉冲处理,然后输注到表达 HPV16 E6/E7 的 TC-1 肿瘤细胞的小鼠模型中。测量 IFN-γ、细胞因子(TNF-α、IL-12、IL-6)表达、抗-E7 抗体和细胞毒性 T 淋巴细胞(CTL)水平。监测不同治疗组小鼠模型的存活率、存活天数和肿瘤体积。数据表明,经腺病毒介导的 SOCS1 沉默增强的 mE7 脉冲 DC 疫苗对同种异体移植肿瘤小鼠模型具有更好的免疫治疗效果。在 HPV16mE7 蛋白脉冲 DC 中沉默 SOCS1 的方法可能为宫颈癌的安全有效免疫治疗提供新策略。

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