Intravenous delivery of oncolytic reovirus

to brain tumor patients immunologically

primes for subsequent checkpoint blockade

2018.02.14
Oncolytic Virus Immunotherapy
• Local injection of modified viruses for tumor cell lysis
• Reovirus, poxvirus, herpes simplex virus (HSV), etc.
• Increased antitumor activity or reduced pathogenicity
• Ex. Promoters that restrict virulence genes to tumor cells
• Tumor cell lysis  TAA release  CD8+ immunity
• T-VEC (Oct 2015): modified HSV (+GM-CSF)

• OV  type I/II IFN  increased PD-L1 expression

Major Problem with OV immunotherapy
• Requires local injection due to rapid clearance of viruses in
system administration
• Careful patient selection
• Technically challenging neurosurgery
• Limited repeat administration
• However, systemic administration should be more effective
due to metastatic nature of cancer
Overview
• IV infusion of reovirus prior to surgical resection of brain
tumors (phase 1b: 9 patients)
• Validation of reovirus presence, function, and T cell
recruitment
• Relationship between OV, IFN, and increased PD-L1
expression
• Sequential treatment using reovirus IV followed by PD-1
antibody blockade
cleaved caspase 3 PD-L1

PD-1
 lymphocytes

Vascular endothelial cells