Generation of anti-tumor response by JAWS II mouse dendritic cells transduced with murine interleukin 12 genes.
Murine dendritic cells (DCs) of the established JAWS II cell line were transduced with a retroviral vector carrying murine interleukin 12 (IL-12) genes (JAWS II/IL-12 cells). The JAWS II/IL-12 cells produced approximately 9-18 ng IL-12 protein/ml/5 x 10(5) cells/48 h and displayed an increased CD80 and CD86 expression as well as major histocompatibility complex antigen up-regulation. The JAWS II/IL-12 cells were used as a temporary source of IL-12 for the immunotherapy of C57BL/6 mice bearing transplantable murine colon carcinoma (MC38). The cell vaccines were administered according to different application schedules into the vicinity of subcutaneously growing palpable MC38 tumors. The JAWS II/IL-12 cells were delivered alone or in combination with JAWS II cells pulsed with MC38 tumor cell lysate (TAg) (JAWS II/TAg cells). The anti-tumor response was estimated as the tumor growth delay--the time (days) required for the tumor to reach a volume of 1 cm3 (TRV), and as the increase in animal life-span (ILS). Mice treated with three consecutive injections of JAWS II/IL-12 or JAWS II/TAg cells responded with moderate tumor growth delay (up to 6.5 and 9.5 days, respectively). After the administration of the JAWS II/IL-12 and JAWS II/TAg cell combination, the TRV was prolonged up to 12.5 days and there was a long-lasting tumor growth delay. Increasing the number of DC-based vaccines to four, resulted in the ILS extension of up to 87% over the control. A similar effect was observed when the vaccine containing the combination of both DC components was delivered prior to the three consecutive injections of JAWS II/IL-12 or JAWS II/TAg cells administered independently. The JAWS II/IL-12 cell vaccination of MC38 tumor-bearing mice was accompanied by an increased percentage of IFN-gamma-producing CD8+ spleen cells. Concluding, JAWS II DCs transduced with IL-12 genes could be used as an adjuvant vaccine for immuno- as well as combined immuno-chemotherapy of experimental tumors.
Pajtasz-Piasecka
Elzbieta
E
Institute of Immunology and Experimental Therapy PAS, Laboratory of Experimental Anticancer Therapy, 53-114 Wroclaw, Poland. pajtasz@iitd.pan.wroc.pl
Rossowska
Joanna
J
Szyda
Anna
A
Krawczenko
Agnieszka
A
Dus
Danuta
D
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D019496:Cancer Vaccines; D014409:Tumor Necrosis Factor-alpha; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D007371:Interferon-gamma