Binz Eike, Berchtold Susanne, Beil Julia, Schell Martina, Geisler Christine, Smirnow Irina, Lauer Ulrich M
Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
German Cancer Consortium (DKTK), DKFZ Partner Site, 72076 Tuebingen, Germany.
Mol Ther Oncolytics. 2017 Apr 19;6:10-21. doi: 10.1016/j.omto.2017.04.001. eCollection 2017 Sep 15.
Oncolytic viruses have proven their therapeutic potential against a variety of different tumor entities both in vitro and in vivo. Their ability to selectively infect and lyse tumor cells, while sparing healthy tissues, makes them favorable agents for tumor-specific treatment approaches. Particularly, the addition of virotherapeutics to already established chemotherapy protocols (so-called chemovirotherapy) is of major interest. Here we investigated the in vitro cytotoxic effect of the oncolytic vaccinia virus GLV-1h68 combined with dual chemotherapy with -paclitaxel plus gemcitabine in four human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, MIA-PaCa-2, and Panc-1). This chemovirotherapeutic protocol resulted in enhanced tumor cell killing in two tumor cell lines compared to the respective monotherapies. We were thereby able to show that the combination of oncolytic vaccinia virus GLV-1h68 with -paclitaxel and gemcitabine has great potential in the chemovirotherapeutic treatment of advanced pancreatic adenocarcinoma. However, the key to a successful combinatorial chemovirotherapeutic treatment seems to be a profound viral replication, as tumor cell lines that were non-responsive to the combination therapy exhibited a reduced viral replication in the presence of the chemotherapeutics. This finding is of special significance when aiming to achieve a virus-mediated induction of a profound and long-lasting antitumor immunity.
溶瘤病毒已在体外和体内证明了其对多种不同肿瘤实体的治疗潜力。它们能够选择性地感染并裂解肿瘤细胞，同时不损伤健康组织，这使其成为肿瘤特异性治疗方法的理想药物。特别是，将病毒疗法添加到已有的化疗方案中（即所谓的化学病毒疗法）备受关注。在此，我们研究了溶瘤痘苗病毒GLV-1h68联合紫杉醇加吉西他滨双重化疗对四种人胰腺腺癌细胞系（AsPc-1、BxPc-3、MIA-PaCa-2和Panc-1）的体外细胞毒性作用。与各自的单一疗法相比，这种化学病毒疗法方案在两种肿瘤细胞系中增强了肿瘤细胞杀伤作用。我们由此能够证明，溶瘤痘苗病毒GLV-1h68与紫杉醇和吉西他滨联合应用在晚期胰腺腺癌的化学病毒治疗中具有巨大潜力。然而，成功的联合化学病毒治疗的关键似乎在于强大的病毒复制，因为对联合疗法无反应的肿瘤细胞系在存在化疗药物的情况下病毒复制减少。当旨在实现病毒介导的深度和持久抗肿瘤免疫诱导时，这一发现具有特殊意义。
