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