A Tumor-Targeted Replicating Oncolytic Adenovirus Ad-TD-nsIL12 as a Promising Therapeutic Agent for Human Esophageal Squamous Cell Carcinoma.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in China and existing therapies have been unable to significantly improve prognosis. Oncolytic adenoviruses (OAds) are novel promising anti-tumor drugs and have been evaluated in several cancers including ESCC. However, the antitumour efficacy of the first generation OAds (H101) as single agent is limited. Therefore, more effective OAds are needed. Our previous studies demonstrated that the novel oncolytic adenovirus Ad-TD-nsIL12 (human adenovirus type 5 with E1ACR2, E1B19K, E3gp19K-triple deletions)harboring human non-secretory IL-12 had significant anti-tumor effect, with no toxicity, in a Syrian hamster pancreatic cancer model. In this study, we evaluated the anti-tumor effect of Ad-TD-nsIL12 in human ESCC. The cytotoxicity of Ad-TD-nsIL12, H101 and cisplatin were investigated in two newly established patient-derived tumor cells (PDCs) and a panel of ESCC cell lines in vitro. A novel adenovirus-permissive, immune-deficient Syrian hamster model of PDCs subcutaneous xenograft was established for in vivo analysis of efficacy. The results showed that Ad-TD-nsIL12 was more cytotixic to and replicated more effectively in human ESCC cell lines than H101. Compared with cisplatin and H101, Ad-TD-nsIL12 could significantly inhibit tumor growth and tumor angiogenesis as well as enhance survival rate of animals with no side effects. These findings suggest that Ad-TD-nsIL12 has superior anti-tumor potency against human ESCC with a good safety profile.