ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma

Ji Young Yoo, Jun Ge Yu, Azeem Kaka, Quintin Pan, Pawan Kumar, Bhavna Kumar, Jianying Zhang, Andrew Mazar, Theodoros N. Teknos, Balveen Kaur, Matthew O. Old

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide, and the 5-year survival rates are among the worst of the major cancers. Oncolytic herpes simplex viruses (oHSV) have the potential to make a significant impact in the targeted treatment of these patients. Here, we tested antitumor efficacy of RAMBO, an oHSV armed with the antiangiogenic Vstat120, alone and in conjunction with ATN-224, a copper chelator against HNSCC in vitro and in vivo animal models. We found that all tested HNSCC cells responded well to virus treatment and were sensitive to RAMBO-mediated oncolytic destruction. In vivo, RAMBO had a significant antiangiogenic and antitumorigenic effect. Physiologic levels of copper inhibited viral replication and HNSCC cell killing. Chelation of copper using ATN-224 treatment significantly improved serum stability of RAMBO and permitted systemic delivery in HNSCC tumor xenografts models. Furthermore, our results show that the combination of ATN-224 and RAMBO strongly inhibits lung metastases in a mouse model of HNSCC. These findings suggest that combining ATN-224 with RAMBO has potential for clinical trials in both early and advanced HNSCC patients.

Original languageEnglish (US)
Article number15008
Pages (from-to)15008
Number of pages1
JournalMolecular Therapy - Oncolytics
Volume2
DOIs
StatePublished - May 20 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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