Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Viruses. 2023 Jan 19;15(2):283. doi: 10.3390/v15020283.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance. Oncolytic viruses have emerged as a new treatment approach and convey their antitumor activity through lysis of cancer cells. The therapeutic efficacy of oncolytic viruses is largely dependent on the induction of immunogenic cell death (ICD) and the subsequent antitumor immune responses. However, the concurrent generation of antiviral immune responses may also limit the a virus' therapeutic window. GoraVir is a new oncolytic adenovirus derived from the Human Adenovirus B (HAdV-B) isolate AdV-lumc007 which was isolated from a gorilla and has demonstrated excellent lytic activity in both in vitro and in vivo models of PDAC. In this study, we characterized the immunostimulatory profile of cancer cell death induced by GoraVir and the concerted cellular antiviral responses in three conventional pancreatic cancer cell lines. While GoraVir was shown to induce late apoptotic/necrotic cell death at earlier time points post infection than the human adenovirus type 5 (HAdV-C5), similar levels of ICD markers were expressed. Moreover, GoraVir was shown to induce ICD not dependent on STING expression and regardless of subsequent antiviral responses. Together, these data demonstrate that GoraVir is an excellent candidate for use in oncolytic virotherapy.
胰腺导管腺癌 (PDAC) 是一种高度侵袭性的恶性肿瘤，表现出无与伦比的治疗抵抗性。溶瘤病毒已成为一种新的治疗方法，通过裂解癌细胞来发挥其抗肿瘤活性。溶瘤病毒的治疗效果在很大程度上取决于诱导免疫原性细胞死亡 (ICD) 和随后的抗肿瘤免疫反应。然而，同时产生的抗病毒免疫反应也可能限制病毒的治疗窗口。GoraVir 是一种新型溶瘤腺病毒，源自从大猩猩中分离出的人腺病毒 B (HAdV-B) 分离株 AdV-lumc007，在 PDAC 的体外和体内模型中均显示出优异的溶瘤活性。在这项研究中，我们研究了 GoraVir 诱导的癌细胞死亡的免疫刺激特征，以及三种常规胰腺癌细胞系中的协同细胞抗病毒反应。虽然 GoraVir 在感染后早期的晚期凋亡/坏死细胞死亡比人腺病毒 5 型 (HAdV-C5) 更早，但表达的 ICD 标志物相似。此外，GoraVir 诱导 ICD 不依赖于 STING 表达，也不依赖于随后的抗病毒反应。总之，这些数据表明 GoraVir 是溶瘤病毒治疗的优秀候选者。
