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Modification of Professional Antigen-Presenting Cells with Small Interfering RNA In vivo to Enhance Cancer Vaccine Potency

Departments of ¹ Pathology, ² Obstetrics and Gynecology, ³ Oncology, ⁴ Pharmacology and Molecular Sciences, ⁵ Neurology, and ⁶ Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland and ⁷ Department of Advanced Materials, Korea Research Institute of Chemical Technology, Daejon, Korea

Requests for reprints: T-C. Wu, Department of Pathology, Johns Hopkins University School of Medicine, Ross 512H, 720 Rutland Avenue, Baltimore, MD 21205. Phone: 410-614-3899; Fax: 443-287-4295; E-mail: wutc{at}jhmi.edu.

RNA interference using small interfering RNA (siRNA) is an effective means of silencing gene expression in cells. Intradermal administration of nucleic acids via gene gun represents an efficient method for delivering nucleic acids to professional antigen-presenting cells in vivo. In this study, we show that the coadministration of DNA vaccines encoding human papillomavirus type 16 E7 with siRNA targeting key proapoptotic proteins Bak and Bax prolongs the lives of antigen-expressing dendritic cells in the draining lymph nodes, enhances antigen-specific CD8⁺ T-cell responses, and elicits potent antitumor effects against an E7-expressing tumor model in vaccinated mice. Our data indicate that intradermal administration of siRNA to manipulate gene expression represents a plausible strategy for modification of the properties of professional antigen-presenting cells in vivo to enhance cancer vaccine potency.

Key Words: Cancer vaccine • Dendritic cell • Immunotherapy • siRNA • DNA vaccine

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