Pancreatic adenocarcinoma is a poorly immunogenic malignancy without effective adjuvant treatment. One strategy for combating this malignancy is using gene transfer technology to augment antitumor immunity. We propose a comparative investigation of tumor vaccine strategies in C57BL/6 mice bearing K-ras-expressing subcutaneous tumors derived from Panc02, a murine pancreatic adenocarcinoma cell line. First, we will construct vectors encoding K-ras and generate K-ras-expressing Panc02 cell lines. Second, we will investigate whether dendritic cells, potent antigen-presenting cells, which express K-ras and secrete GM-CSF can stimulate antitumor immunity against K-ras-expressing Panc02 tumors in mice. Third, we will test K-ras-expressing autologous and allogeneic tumor cell-based vaccines. Finally, we will directly compare these three vaccine strategies to determine which approach will be most useful in gene-based immunotherapy of pancreatic adenocarcinoma in clinical trials.
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| Tseng, Jennifer F; Farnebo, Filip A; Kisker, Oliver et al. (2002) Adenovirus-mediated delivery of a soluble form of the VEGF receptor Flk1 delays the growth of murine and human pancreatic adenocarcinoma in mice. Surgery 132:857-65 |
