Pancreatic cancer is one of the most aggressive malignancies. In order to change its devastating prognosis, a novel therapeutic approach must be developed. The conditionally replicative adenovirus (CRAd) is one such promising therapeutic modality for pancreatic cancer. CRAd clinical trials to date have established the safety of these agents and identified their current limitations, and our laboratory is developing safer and more potent CRAds for therapeutic use. In this proposal, we plan to develop of a new generation pancreatic cancer CRAds with superior therapeutic potency and disease selectivity by exploiting the specific molecular features of this disease itself. We have developed new generation vector modifications which can provide a different level of transduction efficiency, and recent advancements in pancreatic cancer molecular biology have identified several target-worthy molecular features. The CRAds engineered for better potency and target specificity will be outfitted with anti-tumor effectors modifying pancreatic cancer tumor environment. New vectors will be tested not only with mouse subcutaneous and orthotopic xenograft models but also with models showing close relevance to human clinical situations. A hamster syngeneic pancreatic cancer model which allows human adenoviral replication will provide deeper insight into CRAd biology. The CRAd function analysis based on tissue slice technology permits us to evaluate CRAds in patient materials. These assessments will be further strengthened by the non-invasive viral replication monitoring capability we have developed. The development and analysis of next-generation CRAds will precede a clinically meaningful and novel therapy for pancreatic cancer.

Public Health Relevance

The poor prognosis for pancreatic cancer drives our effort to develop new therapeutic modalities. More potent and safer CRAds can be fashioned into a clinically effective therapeutics. Also, detailed analyses of CRAd functionality in clinically relevant models will provide the crucial information required to advance vector design. The outcome of this project will lead to a clinically usable therapeutics for pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA094084-09
Application #
8258802
Study Section
Developmental Therapeutics Study Section (DT)
Program Officer
Arya, Suresh
Project Start
2002-03-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
9
Fiscal Year
2012
Total Cost
$287,621
Indirect Cost
$83,769
Name
University of Minnesota Twin Cities
Department
Surgery
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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