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2004:
Sewell Duane A; Douven Dennis; Pan Zhen-Kun; Rodriguez Alex; Paterson Yvonne
Regression of HPV-positive tumors treated with a new Listeria monocytogenes vaccine.
Archives of otolaryngology--head & neck surgery 2004;
130(
1):.
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. DESIGN: 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. INTERVENTION: 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. CONCLUSION: 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.
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