title: Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity.
abstract: Dendritic cells (DCs) are highly efficient antigen-presenting cells capable of priming both cytotoxic and helper T cells in vivo. Recent studies have demonstrated the potential use of DCs that are modified to carry tumor-specific antigens in cancer vaccines. However, the optimal administration route of DC-based vaccines to generate the greatest anti-tumor effect remains to be determined. This study is aimed at comparing the levels of immune responses and anti-tumor effect generated through different administration routes of DC-based vaccination. We chose the E7 gene product of human papillomavirus (HPV) as the model antigen and generated a stable DC line (designated as DC-E7) that constitutively expresses the E7 gene. Among the three different routes of DC-E7 vaccine administration in a murine model, we found that intramuscular administration generated the greatest anti-tumor immunity compared with subcutaneous and intravenous routes of administration. Furthermore, intramuscular administration of DC-E7 elicited the highest levels of E7-specific antibody and greatest numbers of E7-specific CD4+ T helper and CD8+ T cell precursors. Our results indicate that the potency of DC-based vaccines depends on the specific route of administration and that intramuscular administration of E7-transfected DCs generates the most potent E7-specific anti-tumor immunity.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institution, Baltimore, MD 21287, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Ling
authors.forename: I M
authors.initials: IM
authors.lastname: Shih
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: S I
authors.initials: SI
authors.lastname: Pai
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: R J
authors.initials: RJ
authors.lastname: Kurman
authors.forename: D M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: T C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000821:virology*; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D016233:Immunotherapy, Active / Q000379:methods*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control*
chemical_list: D019496:Cancer Vaccines; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16