title: 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.
  
  
  CONCLUSIONS
  These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV.
authors: Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: M
authors: M
authors: Gil
authors: M
authors: M
authors: Bieniasz
authors: M
authors: M
authors: Seshadri
authors: D
authors: D
authors: Fisher
authors: M J
authors: MJ
authors: Ciesielski
authors: Y
authors: Y
authors: Chen
authors: R K
authors: RK
authors: Pandey
authors: D
authors: D
authors: Kozbor
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy; D014616:Vaccinia virus / Q000502:physiology; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays