title: Regression of HPV-positive tumors treated with a new Listeria monocytogenes vaccine.
abstract: BACKGROUND
  Human papillomavirus (HPV) has been implicated in the pathogenesis of 15% to 23% of head and neck squamous cell carcinomas as well as most oropharyngeal carcinomas. The viral oncoproteins E6 and E7 are expressed in HPV-positive tumor cells and therefore provide ideal targets for tumor immunotherapy. Because of its unique ability to induce a cellular immune response, the intracellular bacteria Listeria monocytogenes has been studied as a potential HPV-positive tumor vaccine.
  
  
  OBJECTIVE
  To present a new recombinant strain of L monocytogenes that is effective in treating HPV-positive tumors in a murine model.
  
  
  METHODS
  A new recombinant L monocytogenes vaccine, Lm-ActA-E7, was designed by transforming an attenuated Listeria strain with an E7 expression cassette. The cassette consists of the HPV-16 E7 sequence fused to the Listeria protein ActA. The resultant strain of bacteria secretes E7 antigen as a fusion protein with ActA.
  
  
  METHODS
  Tumors were established in C57BL/6 mice with a syngeneic HPV-positive cell line prior to treatment with vaccine.
  
  
  METHODS
  The Lm-ActA-E7 vaccine was administered intraperitoneally to the mice 5 days after tumors were established. A booster dose was administered 7 days after the first dose. Tumor progression was measured in 2 dimensions periodically after the vaccination.
  
  
  RESULTS
  In C57BL/6 mice, the administration of Lm-ActA-E7 caused the complete regression of HPV-positive tumors in 6 of 8 mice tested. A cytotoxic T-lymphocyte assay revealed that administration of the vaccine caused the generation of cytotoxic T cells specific for E7.
  
  
  CONCLUSIONS
  Our results demonstrate the ability of a new Listeria-based vaccine to generate a specific antitumor T-cell response and cause the regression of HPV-positive tumors in a murine model.
authors.affiliation: Department of Otorhinolaryngology, University of Pennsylvania School of Medicine, Philadelphia, USA. dsewell@mail.med.upenn.edu
authors.forename: Duane A
authors.initials: DA
authors.lastname: Sewell
authors.forename: Dennis
authors.initials: D
authors.lastname: Douven
authors.forename: Zhen-Kun
authors.initials: ZK
authors.lastname: Pan
authors.forename: Alex
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Paterson
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D008089:Listeria monocytogenes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000032:analysis; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic
chemical_list: D001428:Bacterial Vaccines; D015513:Oncogene Proteins; D014614:Vaccines, Synthetic