Z Gastroenterol 2014; 52 - FV15
DOI: 10.1055/s-0034-1385989

Results of the first study on intraperitoneal virotherapy employing a recombinant vaccinia virus genetically engineered to selectively replicate in and destroy cancer cells

UM Lauer 1, J Beil 1, 2, S Berchtold 1, M Zimmermann 1, U Koppenhöfer 1, M Bitzer 1, NP Malek 1, J Glatzle 3, A Königsrainer 3, R Möhle 4, F Fend 5, C Pfannenberg 6, T Auth 2, T Yu 7, AA Szalay 2, 7, 8
  • 1University Hospital Tübingen, Department of Internal Medicine I, Tübingen, Germany
  • 2Genelux GmbH, Bernried, Germany
  • 3University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Tübingen, Germany
  • 4University Hospital Tübingen, Department of Internal Medicine II, Tübingen, Germany
  • 5University Hospital Tübingen, Institute for Pathology, Tübingen, Germany
  • 6University Hospital Tübingen, Department for Diagnostic and Interventional Radiology, Tübingen, Germany
  • 7Genelux Corporation, San Diego, United States
  • 8Rudolph Virchow Center for Experimental Biomedicine, Department of Biochemistry and Institute for Molecular Infection Biology, Würzburg, Germany

Introduction: GL-ONC1 constitutes a recombinant Vaccinia virus genetically engineered to selectively replicate in and destroy cancer cells. Since GL-ONC1 encodes state-of-the-art marker genes, features of its tumor cell colonization, in-patient replication, and oncolysis can be tracked excellently. We here report our data obtained in patients with peritoneal carcinomatosis (PC) who have been recruited to our ongoing phase I/II virotherapy study (NCT01443260).

Methods: GL-ONC1 is administered intraperitoneally up to 4 times under a standard 3+3 dose escalation design. Virological data and anti-tumor activities are determined by “fluid biopsies” obtained via repetitive paracenteses. Patient samples are collected for pharmacokinetics, pharmacodynamics and viral shedding analysis.

Results: Up to now, 9 patients (exhibiting advanced stage PC from gastric and ovarian cancer, mesothelioma as well as from adeno-CUP) have received 24 doses of GL-ONC1. Adverse events generally have been limited to grade 1/2. No DLT has been reported. Furthermore, no viral shedding has been observed. In 8 out of 9 study patients, effective intraperitoneal infections and in-patient replication of GL-ONC1 as well as subsequent oncolysis (demonstrated by release of GL-ONC1 encoded ß-glucuronidase) have been demonstrated. In addition, it was found that pre-vaccination did not exert any negative impact on all of these processes. All 9 study patients developed neutralizing antibodies against GL-ONC1 (at the earliest on day 8 of treatment cycle 1).

Conclusions: Our data demonstrate that GL-ONC1 is well tolerated when infused intraperitoneally. Importantly, both low and higher doses of intraperitoneally administered GL-ONC1 were found to be capable to infect, replicate in and significantly lyse tumor cells in all four tumor entities being addressed so far. Marker gene-assisted tracking yields important information on safety as well as efficiency of this virotherapeutic approach and therefore is considered as a standard also for other virotherapy studies to be performed in the future.

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