Whole tumor antigen vaccination using dendritic cells: comparison of RNA electroporation and pulsing with UV-irradiated tumor cells.
Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC) based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV) B radiation using a convenient tumor model expressing human papilloma virus (HPV) E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.
Benencia
Fabian
F
Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, PA, USA. benencia@oucom.ohiou.edu
Courrèges
Maria C
MC
Coukos
George
G
D000818:Animals; D000951:Antigens, Neoplasm; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D027383:Papillomaviridae / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014466:Ultraviolet Rays
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012313:RNA