A3: Intravenous delivery of oncolytic REOLYSIN to primary and secondary brain tumours
1Leeds University, Leeds, UK,2Leeds General Infirmary, Leeds, UK,3Oncolytics, Alberta, Canada,4St James’s University Hospital, Leeds, UK
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. Previous data suggest that intra-lesional administration of REOLYSIN® is well tolerated, with early signs of efficacy. 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.
This was 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. Patients were treated with a single infusion of 1x1010 TCID50 of REOLYSIN®. The primary endpoint is the presence of REOLYSIN® in the resected tumours as assessed by immunohistochemistry, RNA in-situ hybridization and retrieval of infectious virions.
9 patients have completed the study to date, including 4 with glioblastoma multiforme, 2 with grade III glioma and 3 brain metastases cases. All resected tumours contained REOLYSIN® RNA and/or protein by IHC or qPCR. 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). The presence of reovirus within tumours was associated with upregulation of PD-L1 on tumour cells. Only one trial patient has died since the beginning of recruitment in September 2013.
We have shown for the first time that an oncolytic virus, REOLYSIN®, infects and replicates in brain tumours following intravenous administration. This trial will pave the way for phase I/II trials and combination studies using REOLYSIN® in this patient group, which are already in development. Upregulation of PD-L1 associated with reovirus in tumour cells provides a rationale for combination treatment of virotherapy with checkpoint blockade antibodies.