Toxicological and bio-distribution profile of a GM-CSF-expressing, double-targeted, chimeric oncolytic adenovirus ONCOS-102 - Support for clinical studies on advanced cancer treatment

PLoS One. 2017 Aug 10;12(8):e0182715. doi: 10.1371/journal.pone.0182715. eCollection 2017.

Abstract

The purpose of this work was to carry out preclinical toxicity and bio-distribution studies required for regulatory approval of a clinical trial application for Phase I clinical studies of ONCOS-102 (Ad5/3-D24-GM-CSF) for therapy of advanced cancers (NCT01598129). The study design, route of administration and dosage differs from the clinical protocol and in more detail, investigate bio-distribution and toxicological profile of ONCOS-102 treatment in animal model. The study was carried out in 300 hamsters divided into nine test groups-three bio-distribution groups and six groups for analysis of toxicity. Hamsters received ONCOS-102 by intracardial, intraperitoneal or subcutaneous injections. Additionally, one group was administered twice a week with intraperitoneal injections of Cyclophosphamide. The control animals were administered with NaCl solution without ONCOS-102 in the same volume and the same way. No adverse effects of repeated administration of ONCOS-102 including body weight, food consumption, hematology and clinical chemistry parameters, histopathology and bio-accumulation were observed in the course of 6-month administration and following 3- month recovery period. All obtained findings indicate the treatment clinically safe.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cricetinae
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Male
  • Mesocricetus
  • Molecular Targeted Therapy
  • Neoplasms / therapy*
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics*
  • Tissue Distribution

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor

Grants and funding

Marie Curie Innovative Training Network (ITN) grant, ADVance (FP7-290002) provided support in the form of salary for author LK. Targovax Oy provided support in the form of salaries for authors LK, TR, AV, SP, LV. Targovax Oy had a role in study design, data collection and analysis, decision to publish, and preparation of the manuscript by supervising, monitoring, funding the study and manuscript preparation. The specific roles of these authors are articulated in the ‘author contributions’ section.