Regression of HPV-positive tumors treated with a new Listeria monocytogenes vaccine.
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.
Sewell
Duane A
DA
Department of Otorhinolaryngology, University of Pennsylvania School of Medicine, Philadelphia, USA. dsewell@mail.med.upenn.edu
Douven
Dennis
D
Pan
Zhen-Kun
ZK
Rodriguez
Alex
A
Paterson
Yvonne
Y
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
D001428:Bacterial Vaccines; D015513:Oncogene Proteins; D014614:Vaccines, Synthetic