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Duane A. Sewell, MD; Dennis Douven, BA; Zhen-Kun Pan, PhD; Alex Rodriguez, BA; Yvonne Paterson, PhD

Arch Otolaryngol Head Neck Surg. 2004;130:92-97.

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.

From the Departments of Otorhinolaryngology (Dr Sewell) and Microbiology (Drs Sewell, Pan, and Paterson and Messrs Douven and Rodriguez), University of Pennsylvania School of Medicine, Philadelphia. The authors have no relevant financial interest in this article.

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