title: Gene therapy with IL-12 induced enhanced anti-tumor activity in fibrosarcoma mouse model.
abstract: Context Immunotherapy is among the most promising modalities for treatment of cancer. Recently, interleukin 12 (IL-12) has been used as an immunotherapeutic agent in cancer gene therapy. IL-12 can activate dendritic cells (DCs) and boost anti-tumor immune responses. Objective In the current study, we have investigated if IL-12 gene therapy can lead to the regression of tumor mass in a mouse model of fibrosarcoma. Material and methods To investigate the therapeutic efficacy of IL-12, WEHI-164 tumor cells were transfected with murine-IL12 plasmids using Lipofectamine. Enzyme linked immunosorbent assay (ELISA) was used to confirm IL-12 expression in transfected cells. The fibrosarcoma mouse model was established by subcutaneous injection of transfected cells to Balb/C mice. Mice were sacrificed and the tumors were extracted. Tumor sizes were measured by caliper. The expression of IL-12 and IFN-γ was studied with real-time PCR and western blotting. The expression of Ki-67(a tumor proliferation marker) in tumor mass was studied by immunohistochemistry staining. Results and discussion The group treated with IL-12 showed a significant decrease in tumor mass volume (P: 0.000). The results of real-time PCR and western blotting showed that IL-12 and IFN-γ expression increased in the group treated with IL-12 (relative expression of IL-12: 1.9 and relative expression of IFN-γ: 1.766). Immunohistochemistry staining showed that Ki-67 expression was reduced in the group treated with IL-12. Conclusion IL-12 gene therapy successfully led to regress of tumor mass in the fibrosarcoma mouse model. This may serve as a candidate therapeutic approach for treatment of cancer.
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Saiedeh
authors.initials: S
authors.lastname: Razi Soofiyani
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Tohid
authors.initials: T
authors.lastname: Kazemi
authors.affiliation: b Department of Pharmaceutical and Food Control, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Lotfipour
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Mohammad Hosseini
authors.affiliation: c Biotechnology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: b Department of Pharmaceutical and Food Control, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Hallaj-Nezhadi
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D018664:Interleukin-12
keywords: Gene therapy; IL-12; in vivo; tumor