Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity.
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.
Wang
T L
TL
Department of Pathology, The Johns Hopkins Medical Institution, Baltimore, MD 21287, USA.
Ling
M
M
Shih
I M
IM
Pham
T
T
Pai
S I
SI
Lu
Z
Z
Kurman
R J
RJ
Pardoll
D M
DM
Wu
T C
TC
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*
D019496:Cancer Vaccines; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16