Gastrointestinal cancer represent one of the major reasons for tumor related death in the United States. Current treatment options are limited to surgery, chemotherapy, radiation therapy and molecular targeted therapy and new treatment options are urgently needed. We have currently two clinical trials open for patients with advanced hepatocellular carcinoma. In these trials we evaluate the efficacy of a vascular targeting agent, Trc105. Trc 105 is a monoclonal antibody which binds to CD105 (endoglin), which is highly expressed on tumor infiltrating endothelial cells. In another trial, we are testing the drug combination of cetuximab and AZD6244, a MEK inhibitor. This trial is conducted in collaboration with a site at the University of Wisconsin. Finally we plan to open a trial in which we test an immune based approach in patients with advanced pancreatic cancer, who have failed standard chemotherapy. In this multicenter trial patients will be treated with a combination of GVAX (a GM-CSF expressing allogeneic cell line) and Listeria monocytogenes expressing mesothelin. Fianlly we are in the process of opening another study using an antibody against a target in pancreatic cancer cells as a 2nd line treatment as well as an anti-sense molecule against iEF4A in combination with irinotecan in patients with colon cancer..

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011343-03
Application #
8553119
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$56,140
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Brown, Zachary J; Yu, Su Jong; Heinrich, Bernd et al. (2018) Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma. Cancer Immunol Immunother 67:1305-1315
Alter, Harvey; Block, Timothy; Brown, Nathaniel et al. (2018) A research agenda for curing chronic hepatitis B virus infection. Hepatology 67:1127-1131
Khanna, Swati; Graef, Suzanne; Mussai, Francis et al. (2018) Tumor-Derived GM-CSF Promotes Granulocyte Immunosuppression in Mesothelioma Patients. Clin Cancer Res 24:2859-2872
Ziegler, Paul K; Bollrath, Julia; Pallangyo, Charles K et al. (2018) Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis. Cell 174:88-101.e16
Greten, Tim F; Korangy, Firouzeh (2018) CDK20 inhibition and immune checkpoint blockade: bringing cancer biology and tumour immunology together to develop novel treatment options for HCC. Gut 67:783-784
Ma, Chi; Zhang, Qianfei; Greten, Tim F (2018) Nonalcoholic fatty liver disease promotes hepatocellular carcinoma through direct and indirect effects on hepatocytes. FEBS J 285:752-762
Greten, Tim F (2018) The ABC of adaptive immunity in liver cancer. Hepatology 68:777-779
Ma, Chi; Han, Miaojun; Heinrich, Bernd et al. (2018) Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360:
Block, Timothy M; Alter, Harvey; Brown, Nathaniel et al. (2018) Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop. Antiviral Res 150:93-100
Brown, Zachary J; Heinrich, Bernd; Greten, Tim F (2018) Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat Rev Gastroenterol Hepatol :

Showing the most recent 10 out of 49 publications