Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

Abstract

Background:Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice.Methods:The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay.Results:Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue.Conclusion:These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV.

CXCL12/CXCR4 Blockade by Oncolytic Virotherapy Inhibits Ovarian Cancer Growth by Decreasing Immunosuppression and Targeting Cancer-Initiating Cells

“…Tumor progression was monitored by bioluminescence imaging. For experiments in CAOV2-challenged SCID mice, animals were treated with a lower titer of the virus (2.5 × 10 7 PFU) and vaccinia virus-specific antibodies (100 μg of antibodies with neutralizing titer of 1 : 100) were delivered 7 days after viral challenge to inhibit spreading infection as described (47). Control mice received PBS or UV-inactivated virus.…”

The role of photodynamic therapy in overcoming cancer drug resistance

“…First, low-dose vascular PDT can be used to transiently enhance blood vessel permeability, enabling an increased delivery of macromolecular and nanoparticle drug payloads to the tumor 49–51 . Although this phenomenon has been known for over a decade, more recently it has been termed “super-enhanced permeability and retention (SUPR)”, in reference to further boosting the enhanced permeability and retention (EPR) effect well known in tumor biology 52 .…”

“…An early demonstration of this concept by Henderson’s group showed dramatic enhancements in the delivery of fluorescent microspheres (0.1–2 µm) and of a liposome-encapsulated formulation of doxorubicin (Doxil) to subcutaneous tumors 49 . This strategy has also been applied to enhance oncolytic virus accumulation in subcutaneous tumor models 51 .…”

Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases

“…The changes in tumor vasculature after treatments with the armed and OVV-EGFP viruses were also reflected in tumor perfusion visualized by accumulation of fluorescence beads (39). Fluorescence microscopy of tumor sections revealed a relatively uniform distribution of fluorescence beads in the periphery and core of control tumors (Fig.…”