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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Generation of anti-tumor response by JAWS II mouse dendritic cells transduced with murine interleukin 12 genes.
Oncology Reports 2007 May
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.
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