Listeria Vaccines for Pancreatic Cancer
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease that is notoriously resistant to standard therapies including chemotherapy. This is due in part to a tumor microenvironment that impedes drug delivery. However, leukocytes actively infiltrate tumors. Within the tumor microenvironment, macrophages are the dominant leukocyte and are involved in orchestrating an environment conducive to tumor growth. To reverse pro-tumor activity by leukocytes in PDA, we are investigating Listeria monocytogenes, a facultative intracellular bacterium that infects macrophages and activates them with anti-tumor activity while stimulating productive anti-tumor adaptive immunity. In our studies, we are using the KrasG12D;Trp53R172H;Pdx-1Cre (KPC) mouse model of PDA. Preliminary findings show that macrophages adoptively transferred to KPC mice selectively traffick to tumors with fibrosis. We are now examining the anti-tumor impact of adoptively transferred macrophages activated with Listeria by-products. We have also explored the capacity of Listeria vaccines to induce anti-tumor T cell immunity in the KPC model. We have found that Listeria vaccines produce little impact on late-stage tumors with an absence of T cell infiltration into tumor tissue but do appear to have non-antigen specific anti-stromal effects. We are now investigating the anti-stromal activity observed and the mechanism by which T cells fail to infiltrate tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA600605
Entities
People
- Gregory L Beatty
- Patrick Guirnalda
- Santiago L. Luque
Organizations
- University of Pennsylvania