BACKGROUND The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and presented in the right context. METHODS We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients. RESULTS We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3+ T-reg cells in vitro. CONCLUSIONS This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients.

中文翻译：

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一种使用重组腺相关病毒和p38激酶阻滞转导的树突状细胞有效产生抗原特异性效应T细胞的新方法。

背景技术卵巢癌的标准治疗策略的无效性通过该恶性病的持久不良预后反映出来。由于可能具有出色的特异性，敏感性和长期记忆力，因此只要能够在正确的环境中鉴定并呈递适当的抗原，免疫疗法便可以为疾病的持久控制提供另一种方式。方法我们测试了一种新颖的树突状细胞疫苗制剂，该制剂可在体外，卵巢癌鼠模型中体内和在体外使用来自患者的人类细胞对自体抗原特异性T细胞进行重编程。结果我们显示，用p38 MAPK抑制剂处理并用表达精子蛋白（Sp）17的重组腺病毒相关载体（AAV）转导的树突状细胞（DC）在产生针对卵巢癌细胞的抗原特异性T细胞细胞毒性反应中非常有效。此外，这些DC增强了效应T细胞的分化，同时降低了Foxp3 + T-reg细胞的体外频率。结论这项工作为将药理学上重新编程的DC转化为临床试验提供了理论依据，以预防高危卵巢癌患者的肿瘤复发和进展。