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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA088058-04
Application #
6633834
Study Section
Special Emphasis Panel (ZRG1-CONC (01))
Program Officer
Wu, Roy S
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2003
Total Cost
$398,129
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218