title: Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine.
abstract: Genetically modified tumour cells producing cytokines such as interleukin 12 (IL-12) are potent activators of the antitumour immune responses and represent a promising therapeutic modality when combined with chemotherapy. The objective of this study was to examine whether IL-12-producing cellular vaccines can augment chemotherapy of human papilloma virus (HPV) 16-associated murine tumours with the cytostatic agent gemcitabine (GEM). We found that peritumoral administration of IL-12-producing tumour vaccines enhanced the effect of cytoreductive therapy with GEM both in non-metastasizing murine carcinoma TC-1 and in metastasizing murine carcinoma MK16. The percentage of mice with MK16 metastases and the number of lung metastatic nodules was substantially decreased. In another clinically relevant setting, surgical minimal residual tumour disease, the administration of IL-12-producing tumour vaccine and GEM after the MK16 tumour surgery reduced the percentage of mice with tumour recurrences; similarly, the percentage of metastasis-bearing mice and the number of metastatic nodules was decreased. Tumour inhibitory effects exerted by GEM plus IL-12 were associated with high production of interferon-γ (IFNγ) by splenocytes. Our results suggest that the IL-12-producing vaccine can enhance the effect of GEM chemotherapy in some HPV16-associated murine tumour models.
authors.affiliation: Institute of Molecular Genetics vvi, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Mikyšková
authors.forename: Marie
authors.initials: M
authors.lastname: Indrová
authors.forename: Jana
authors.initials: J
authors.lastname: Símová
authors.forename: Jana
authors.initials: J
authors.lastname: Bieblová
authors.forename: Jan
authors.initials: J
authors.lastname: Bubeník
authors.forename: Milan
authors.initials: M
authors.lastname: Reiniš
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000494:pharmacology*; D002469:Cell Separation; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D052162:Human papillomavirus 16; D018664:Interleukin-12 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D003841:Deoxycytidine; D018664:Interleukin-12; D000093542:Gemcitabine