title: Adenoviral-based immunotherapy provides local disease control in an orthotopic murine model of esophageal cancer.
abstract: Despite recent advances in the development of novel therapies, esophageal carcinoma remains an aggressive cancer associated with a poor prognosis. The lack of a high throughput, reproducible syngeneic animal model that replicates human disease is partly responsible for the paucity of novel therapeutic approaches. In this report, we present the first successful syngeneic, orthotopic model for esophageal cancer. This model was used to test an established adenoviral-based tumor vaccine. We utilized a murine esophageal cancer cell line established from the ED-L2-cyclin D1;p53 mouse that was transduced to express a viral tumor antigen, the Human Papilloma Virus (HPV) E7 protein. The tumor was established in its natural microenvironment at the gastroesophageal junction. Tumor growth was consistent and reproducible. An adenoviral vaccine to E7 (Ad.E7) induced an E7-specific population of functionally active CD8 T cells that trafficked into the tumors and retained cytotoxicity. Ad.E7 vaccination reduced local tumor growth and prolonged overall survival. These findings suggest that orthotopic tumor growth is a reasonable preclinical model to validate novel therapies.
authors.affiliation: *Department of Surgery, Division of Thoracic Surgery †Department of Medicine, Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: Jon G
authors.initials: JG
authors.lastname: Quatromoni
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Predina
authors.forename: Pratik
authors.initials: P
authors.lastname: Bhojnagarwala
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Judy
authors.forename: Jack
authors.initials: J
authors.lastname: Jiang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: De Jesus
authors.forename: Veena
authors.initials: V
authors.lastname: Kapoor
authors.forename: Guanjun
authors.initials: G
authors.lastname: Cheng
authors.forename: Olugbenga T
authors.initials: OT
authors.lastname: Okusanya
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Eruslanov
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16