title: Combined E7-dendritic cell-based immunotherapy and human sodium/iodide symporter radioiodine gene therapy with monitoring of antitumor effects by bioluminescent imaging in a mouse model of uterine cervical cancer.
abstract: Using a uterine cervical cancer cell line expressing human papillomavirus (HPV) 16 E7 antigen and bioluminescent imaging (BLI), we evaluated the therapeutic potential of combined immunotherapy using transfected dendritic cells (DC-E7) and human sodium/iodide symporter (hNIS) radioiodine gene therapy in a xenograft animal cancer model. Dendritic cells expressing either E7 antigen (DC-E7) or no-insert (DC-no insert) were made for immunization materials, and murine uterine cervical cancer cell line coexpressing E7, firefly luciferase, hNIS, and EGFP genes (TC-1/FNG) were prepared for the animal tumor model. C57BL/6 mice were divided into five therapy groups (phosphate-buffered saline [PBS], DC-no insert, DC-E7, I-131, and DC-E7+I-131 groups). Single therapy with either DC-E7 or I-131 induced greater retardation in tumor growth compared with PBS or DC-no insert groups, and it resulted in some tumor-free mice (DC-E7 and I-131 groups, 40% and 20%, respectively). Combination therapy with DC-E7 and I-131 dramatically inhibited tumor growth, thus causing complete disappearance of tumors in all mice, and these effects were further confirmed by BLI in vivo. In conclusion, complete disappearance of the tumor was achieved with combined DC-E7 vaccination and hNIS radioiodine gene therapy in a mouse model with E7-expressing uterine cervical cancer, and serial BLIs successfully demonstrated antitumor effects in vivo.
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Jeon
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Lee
authors.forename: You La
authors.initials: YL
authors.lastname: Lee
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Hwang
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
authors.forename: Jeoung-Hee
authors.initials: JH
authors.lastname: Ha
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D027981:Symporters / Q000235:genetics*; D014162:Transfection / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000099209:Sodium-Iodide Symporters
chemical_list: D019496:Cancer Vaccines; D049452:Green Fluorescent Proteins; D007457:Iodine Radioisotopes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C059731:oncogene protein E7, Human papillomavirus type 16