由于复发和化疗耐药，目前标准治疗对卵巢癌的疗效不够明显。因此，我们旨在找到一种有效的方法改善卵巢癌的预后和治疗。NG34ScFvPD-1是一种改良的溶瘤性单纯疱疹病毒NG34菌株，其表达抗编程性细胞死亡蛋白1（PD-1）的单链抗体（ScFvPD-1）。我们评估了其在小鼠卵巢癌模型中的疗效和调节机制。采用酶联免疫吸附法和西方印迹技术测量蛋白质表达量，使用细胞毒性和复制实验检查NG34ScFvPD-1引起的溶瘤作用，并评估其在体外调节卵巢癌细胞凋亡的机制。我们评估了NG34ScFvPD-1与磷酸肌醇3-激酶（PI3K）抑制剂联合应用的抗肿瘤免疫力和治疗效力。我们发现，NG34ScFvPD-1感染的卵巢癌细胞表达和分泌ScFvPD-1，能够结合小鼠PD-1。ScFvPD-1序列的插入没有抑制NG34ScFvPD-1的溶瘤活性，在体外通过caspase依赖性途径诱导卵巢癌细胞凋亡，并激活PI3K / AKT信号通路。NG34ScFvPD-1和PI3K抑制剂之间存在协同作用，这种联合应用能够抑制肿瘤发展、延长生存时间并激发强大的抗肿瘤免疫力。因此，PI3K的抑制增强了NG34ScFvPD-1对卵巢癌诱导的强大抗肿瘤免疫力。©2023。作者，独家授权Springer-Verlag GmbH Austria，Springer Nature的一部分。

Due to recurrence and resistance to chemotherapy, the current standard therapeutics are not fully effective against ovarian cancer. Therefore, we aimed to find an effective approach to improve the prognosis and therapy of ovarian cancer. NG34ScFvPD-1 is a modified oncolytic herpes simplex virus NG34 strain that expresses a single-chain antibody against programmed cell death protein 1 (PD-1) (ScFvPD-1). We assessed its efficacy and its regulatory mechanism in a mouse model of ovarian cancer. Enzyme-linked immunosorbent assay and western blot techniques were used to measure protein expression. Oncolysis caused by NG34ScFvPD-1 was examined using cytotoxicity and replication assays. The mechanism by which NG34ScFvPD-1 regulates apoptosis of ovarian cancer cells in vitro was also evaluated. We assessed the antitumor immunity and therapeutic potency of NG34ScFvPD-1 in combination with a phosphoinositide 3-kinase (PI3K) inhibitor. We found that NG34ScFvPD-1-infected ovarian cancer cells expressed and secreted ScFvPD-1, which bound mouse PD-1. The insertion of the ScFvPD-1 sequence did not inhibit the oncolytic activity of NG34ScFvPD-1, which induced apoptosis of ovarian cancer cells via the caspase-dependent pathway in vitro and activated the PI3K/AKT signaling pathway. Synergy was observed between NG34ScFvPD-1 and a PI3K inhibitor, and the combination was able to suppress tumor development, to prolong survival, and to elicit potent antitumor immunity. Thus, inhibition of PI3K enhanced the potent antitumor immunity induced by NG34ScFvPD-1 against ovarian cancer.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.