Z Gastroenterol 2015; 53 - KG065
DOI: 10.1055/s-0035-1559091

Chemovirotherapy – Improving the clinical outcome of advanced pancreatic adenocarcinoma by combining the oncolytic vaccinia virus GLV-1h68 with the dual chemotherapy nab-Paclitaxel + gemcitabine

E Binz 1, S Berchtold 1, C Geisler 1, I Smirnow 1, N Malek 1, U Lauer 1
  • 1Medical University Hospital Tuebingen, Department of Internal Medicine I: Division of Hepatology, Gastroenterology, Infectiology, Tuebingen, Deutschland

Background: 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 a favorable agent in specific tumor treatment.

The collected evidence suggests that only in combination with already established forms of treatment their true therapeutic potential can be unlocked, preferably in combination with chemotherapeutics (so called chemovirotherapy). Due to the fact that the mechanisms of action of these two distinct approaches differ greatly the clinical outcome of current treatment regimens might be enhanced while preventing the induction of secondary acquired resistances.

Methods: We investigated in vitro the cytotoxic effect of the combination of oncolytic vaccinia virus GLV-1h68 (also known as GL-ONC1) with the chemotherapeutics nab-Paclitaxel and gemcitabine in 4 well-characterized cell lines of pancreatic adenocarcinoma (AsPc-1, BxPc-3, MIA-PaCa-2, Panc-1).

Remaining tumor cell mass and cell viability after chemovirotherapeutic treatment were analyzed by Sulforhodamine B (SRB) and CellTiter-Blue assay. In addition, we also examined the effect of the respective chemotherapeutic agents on viral replication as determined by viral growth curves.

Results: All 4 pancreatic carcinoma cell lines could be killed successfully by any of the used agents in a dose dependent manner. Moreover, in 2 out of 4 cell lines the combination of GLV-1h68 with the dual chemotherapy nab-Paclitaxel + gemcitabine resulted in an enhanced tumor cell kill compared to the respective monotherapies. Interestingly viral replication remained potent in the same cell lines, in which an elevated response after combinatory treatment was seen, while it was diminished in the others.

Discussion: We were able to show that the combination of oncolytic vaccinia virus GLV-1h68 with the chemotherapeutics nab-Paclitaxel and gemcitabine has great potential in the chemovirotherapeutic treatment of advanced pancreatic adenocarcinoma. Key to a successful combinatory treatment seems to be a strong virus replication, unhindered by the chemotherapeutics given in combination.