| Autor: |
Ralph C. Anth, G. SivaKumar, Julia V. Cockle, Adel Jebar, G. Nuovo, Martin Fuller, R. Corns, Emma West, David Taggart, Elizabeth S. Appleton, Fiona Errington, Matthew C. Coffey, P. Van Hille, Ailsa Rose, Ryan K. Mathew, Karen Scott, Stephen Griffin, Gemma Migneco, Simon Thomson |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Popis: |
INTRODUCTION: Oncolytic viruses preferentially replicate in cancer cells and kill them through direct cytotoxicity and/or immune mediated cell destruction. REOLYSIN® is a proprietary isolate of reovirus type 3 Dearing. In previous trials using intra-lesional administration REOLYSIN® was well tolerated, and there were early signs of efficacy. However, intravenous delivery is a less invasive means of administration that would permit more frequent dosing. This trial aims to identify whether REOLYSIN® can infect primary and secondary brain tumours following intravenous administration. METHOD: This is an open-label, non-randomised study of intravenous REOLYSIN® administered to patients prior to planned surgery for recurrent high-grade glioma or metastatic brain tumours. 12 patients will be treated with a single infusion of 1x1010 TCID50 of REOLYSIN®. The primary objective is the presence of REOLYSIN® in the resected tumours as assessed by immunohistochemistry, RNA in-situ hybridization and retrieval of infectious virions. RESULTS: 9 patients have completed the study to date, including 4 glioblastoma multiforme, 2 grade III glioma and 2 brain metastases cases. 3 of 4 resected GBM patient tumours and both Gd III gliomas contained REOLYSIN® RNA and/or protein. There was evidence for REOLYSIN® productive infection in 8 of the 9 treated tumours. Grade 3-4 adverse reactions were neutropaenia (1 patient) and lymphopaenia (3 patients). CONCLUSION: We have shown for the first time that an oncolytic virus, REOLYSIN®, infects and replicates in primary and secondary brain tumours following intravenous administration. This trial will pave the way for phase I/II trials and combination studies using REOLYSIN® in brain tumour patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
