Chemovirotherapy for pancreatic cancer: Gemcitabine plus oncolytic measles vaccine virus

May,Verena; Berchtold,Susanne; Berger,Alexander; Venturelli,Sascha; Burkard,Markus; Leischner,Christian; Malek,Nisar  P.; Lauer,Ulrich  M.

doi:10.3892/ol.2019.10901

Chemovirotherapy for pancreatic cancer: Gemcitabine plus oncolytic measles vaccine virus

Authors:
- Verena May
- Susanne Berchtold
- Alexander Berger
- Sascha Venturelli
- Markus Burkard
- Christian Leischner
- Nisar P. Malek
- Ulrich M. Lauer
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Affiliations: Department of Internal Medicine I (Gastroenterology, Gastroenterologic Oncology, Hepatology, Infectiology and Geriatric Medicine), University Hospital Tuebingen, D‑72076 Tuebingen, Germany, Department of Internal Medicine VIII (Medical Oncology and Pneumology), University Hospital Tuebingen, D‑72076 Tuebingen, Germany, Boehringer Ingelheim Pharma GmbH and Co. KG, D‑88397 Biberach/Riss, Germany, Department of Vegetative and Clinical Physiology, University Hospital Tuebingen, D‑72076 Tuebingen, Germany
Published online on: September 20, 2019 https://doi.org/10.3892/ol.2019.10901
Pages: 5534-5542

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Abstract

Oncolytic virotherapy with vaccine viruses employs replicative vectors, which quite selectively infect tumor cells leading to massive virus replication followed by subsequent profound tumor cell death (oncolysis). Measles vaccine virus (MeV) has already shown great oncolytic activity against different types of cancers, including pancreatic cancer. Gemcitabine is a first line chemotherapeutic drug used for pancreatic cancer in palliative treatment plans. Furthermore, this drug can be used to induce senescence, a permanent cell cycle arrest, in tumor cells. In our preclinical work, three well‑characterized immortalized human pancreatic cancer cell lines were used to investigate the combinatorial effect of MeV‑based virotherapy together with the chemotherapeutic compound gemcitabine. Viability assays revealed that the combination of only small amounts of MeV together with subtherapeutic concentrations of gemcitabine resulted in a tumor cell mass reduction of >50%. To further investigate the replication of the oncolytic MeV vectors under these distinct combinatorial conditions, viral growth curves were generated. As a result, viral replication was found to be only slightly diminished in the presence of gemcitabine. As gemcitabine induces senescence, the effect of MeV on that phenomenon was explored using a senescence‑associated β‑galactosidase assay. Notably, gemcitabine‑induced tumor cell senescence was not impaired by MeV. Accordingly, the chemovirotherapeutic combination of gemcitabine plus oncolytic MeV constitutes a novel therapeutic option for advanced pancreatic carcinoma that is characterized by the mutual improvement of the effectiveness of each therapeutic component.

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