Yu Wentao, Qu Hong, Cao Guangming, Liu Chongdong, Deng Haiteng, Zhang Zhenyu
Department of Obstetrics & Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):13-19. doi: 10.1016/j.bbrc.2017.10.094. Epub 2017 Oct 20.
Approximately 80% of ovarian cancer (OC) is diagnosed at late stages, and most patients die within 5 years of diagnosis due to recurrence or drug resistance. Novel treatments are required to improve patient survival. Immune therapy against cancer is promising; however, therapeutic vaccination has been limited by the inability of tumor antigens to induce effective immune responses. Chloride intracellular channel 1 (CLIC1) was previously identified as a possible tumor marker for OC. In this study, we constructed a recombinant protein by conjugating the extracellular domain of CLIC1 to the carboxyl terminus of Mycobacterium tuberculosis heat shock protein 70 (MtHsp70). Human dendritic cells (DCs) derived from cortical blood were pulsed with the fusion protein, and the antitumor effect of human cytotoxic T lymphocytes (CTLs) stimulated by autologous DCs was assessed in NOG mice. MtHsp70-CLIC1 promoted the phenotypic maturation of human DCs and the secretion of Th1-associated cytokines in vitro. MtHsp70-CLIC1-stimulated CTLs generated a CLIC1-specific immune response both in vitro and in vivo. These results indicate that DCs pulsed with MtHsp70-CLIC1 can enhance antitumor immunity against OC, providing a novel immune therapeutic strategy.
大约80%的卵巢癌（OC）在晚期被诊断出来，大多数患者在诊断后5年内因复发或耐药而死亡。需要新的治疗方法来提高患者的生存率。抗癌免疫疗法很有前景；然而，治疗性疫苗接种一直受到肿瘤抗原无法诱导有效免疫反应的限制。氯离子细胞内通道1（CLIC1）先前被确定为OC的一种可能的肿瘤标志物。在本研究中，我们通过将CLIC1的胞外结构域与结核分枝杆菌热休克蛋白70（MtHsp70）的羧基末端偶联构建了一种重组蛋白。用融合蛋白刺激源自皮质血的人树突状细胞（DCs），并在NOG小鼠中评估由自体DCs刺激的人细胞毒性T淋巴细胞（CTLs）的抗肿瘤作用。MtHsp70-CLIC1在体外促进了人DCs的表型成熟和Th1相关细胞因子的分泌。MtHsp70-CLIC1刺激的CTLs在体外和体内均产生了CLIC1特异性免疫反应。这些结果表明，用MtHsp70-CLIC1刺激的DCs可以增强针对OC的抗肿瘤免疫力，提供了一种新的免疫治疗策略。
