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

Molecular Therapy: Oncolytics (Jan 2015)

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

Affiliations

Ji Young Yoo: Department of Neurological Surgery, Dardinger Laboratory for Neuro-Oncology and Neurosciences, The Ohio State University Comprehensive Cancer Center and Wexner Medical Center, Columbus, Ohio, USA
Jun-Ge Yu: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
Azeem Kaka: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
Quintin Pan: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
Pawan Kumar: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
Bhavna Kumar: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
Jianying Zhang: Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA
Andrew Mazar: Chemistry of Life Processes Institute and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois, USA
Theodoros N Teknos: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
Balveen Kaur: Department of Neurological Surgery, Dardinger Laboratory for Neuro-Oncology and Neurosciences, The Ohio State University Comprehensive Cancer Center and Wexner Medical Center, Columbus, Ohio, USA
Matthew O Old: Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA

Journal volume & issue: Vol. 2

Abstract

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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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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