Testing Treatment of PDAC

Testing therapies that alter the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC)

Full Project Name:Treatment of PDAC with Combined Immunotherapy, Nox Inhibition, & Altered Chemokine SignalingPrincipal Investigator:Bryon D. Johnson, PhD, MedicineCo-Investigator:Michael B. Dwinell, PhD, Microbiology and ImmunologyAward Amount:$200,000

Award Date

January2016

Project Duration:24 months

Project Description Narrative:

Milwaukee County has one of the highest rates of pancreatic cancer mortality in the U.S., 15% higher than the national average. Locally and nationwide, there is a critical need for new treatments to limit pancreatic cancer progression. Through this award, a research team will investigate the potential of immune therapy to halt pancreatic cancer progression when used in combination with repurposed FDA-approved Nox inhibitors and a novel immune cell "homing" molecule, testing therapies that alter the normal cells surrounding a tumor (the tumor macroenvironment) in pancreatic ductal adenocarcinoma (PDAC) so that tumor-killing immune cells can reach the tumor and be activated to kill cancer cells.

Outcomes & Lessons Learned:

Enabled research team to investigate the potential of immune therapy to halt pancreatic cancer progression when used in combination with repurposed FDA-approved Nox inhibitors and a novel immune cell homing molecule produced at MCW
Completed a series of studies to improve detection of tumor reactive lymphocytes in pancreatic cancer. These approaches include detection of T cells within the central immune tissues (bone marrow), peripheral immune tissues (liver, spleen) and pancreatic tumor parenchyma. The team discovered that recombinant chemokines continue to have powerful use as a biologic therapy, with effects on tumor cells and tumor reactive T cells. While these results have been largely in preclinical animal models, they should be readily translatable to the clinic