ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma.
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.
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.
Ji Young
JY
Yoo
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.
Jun-Ge
JG
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
A
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
Q
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
P
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
B
Kumar
Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University , Columbus, Ohio, USA.
Jianying
J
Zhang
Chemistry of Life Processes Institute and Robert H. Lurie Comprehensive Cancer Center, Northwestern University , Evanston, Illinois, USA.
Andrew
A
Mazar
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.
Theodoros N
TN
Teknos
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.
Balveen
B
Kaur
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.
Matthew O
MO
Old