Pancreatic adenocarcinoma (pancreatic cancer) is the fifth leading cause of cancer death in the U.S. with a case-fatality rate greater than 90 percent. At advanced stages, radiation and chemotherapy are only palliative with small effects on disease- free survival following pancreaticoduodenectomy. Moreover, no methods are available for primary prevention or early screening. Therefore, more effective therapies are urgently needed. Paracrine cytokine tumor vaccines are a novel approach for activating antitumor immunity. This approach can cure mice with low burdens of established tumor, a model that simulates the micro-metastatic disease that is typically encountered in patients. We recently completed a phase I trial of an allogeneic tumor vaccine genetically modified to secrete the cytokine, GM- CSF in patients with resectable pancreatic cancer. Not only was the vaccine well tolerated, but it appeared to provoke dose- dependent activation of immune response and prolongation of disease-free survival. These findings warranting immediate evaluation in a phase II study to determine the vaccine's true benefit. This proposed phase II trial will test the hypothesis that an allogeneic, paracrine cytokine-secreting tumor vaccine can produce significant improvements in disease-free and overall survival in patients with surgically resectable pancreatic adenocarcinoma. Trial endpoints will include: 1) induction of antitumor immune responses including delayed type hypersensitivity against autologous tumor cells and in vitro tumor-specific T cell activity, 2) further characterization of vaccine-related toxicities. Fifty patients with stage 1, 2 or 3 pancreatic cancer who have undergone pancreaticoduodenectomy will be enrolled. In addition, in vitro T cell lines will be developed using lymphocyte and tumor specimens obtained from patients following vaccination and used to identify and characterize the antigens against which the immune response is generated. If successful, this trial will not only represent a major advance in the treatment of pancreatic cancer, but will also spur the development of tumor vaccine for other solid tumors (e.g. breast and prostate). In addition, characterization of pancreatic tumor antigens may lead to the development of recombinant vaccines that can more efficiently activate antitumor immunity.
| Lutz, Eric; Yeo, Charles J; Lillemoe, Keith D et al. (2011) A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. Ann Surg 253:328-35 |
| Zheng, Lei; Foley, Kelly; Huang, Lanqing et al. (2011) Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer. PLoS One 6:e19390 |
| Laheru, Dan; Lutz, Eric; Burke, James et al. (2008) Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 14:1455-63 |
