Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model.

Background: Tumor-specific cytotoxic T lymphocytes (CTL) can be
activated in vivo by vaccination with dendritic cells (DC).
However, clinical responses to DC-based vaccination have only been
observed in a minority of patients with solid cancer. Combination
with other treatment modalities such as chemotherapy may overcome
immunoresistance of cancer cells. We have previously shown that
gemcitabine sensitizes human pancreatic carcinoma cells against
CTL-mediated lysis. Here, we used a murine pancreatic carcinoma
model to investigate whether combination with gemcitabine increases
therapeutic efficacy of DCbased vaccination. Methods: Bone
marrow-derived DC from C57BL/6 mice were loaded with UV-irradiated,
syngeneic Panc02 carcinoma cells and were administered
subcutaneously. For prophylactic vaccination, mice were vaccinated
three times in weekly intervals prior to tumor challenge with
Panc02 cells. Therapeutic vaccination was started when tumors
formed a palpable nodule. Gemcitabine was administered
intraperitoneally twice weekly. Results: Prophylactic DC-based
vaccination completely prevented subcutaneous and orthotopic tumor
development and induced immunological memory as well as tumor
antigen-specific CTL. In the subcutaneous tumor model, therapeutic
DC-based vaccination was equally effective as gemcitabine (14 % vs.
17 % survival at day 58 after tumor challenge; controls: 0 %).
Combination of the two strategies significantly increased survival
of tumor-bearing mice (50 % at day 58 after tumor challenge).
DC-based vaccination also prevented death from pulmonary
metastatization after i.v.-injection of Panc02 cells. Conclusion:
DC-based immunotherapy may not only be successfully combined with
gemcitabine for the treatment of advanced pancreatic carcinoma, but
may also be effective in preventing local recurrence or
metastatization in tumor-free patients.