Title:The Development of Oncolytic Adenovirus Therapy in the Past and Future - For the Case of Pancreatic Cancer
Volume: 18
Issue: 2
Author(s): Mizuho Sato-Dahlman and Masato Yamamoto*
Affiliation:
- Division of Basic and Translational Medicine, Department of Surgery, University of Minnesota, MN,United States
Keywords:
Oncolytic Adenovirus, Cox-2 promoter, Fiber-modified Ad, Pancreatic cancer, Adenovirus library screening.
Abstract: Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments
for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy
strategies may provide new options for the treatment of various cancers including pancreatic cancer.
Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal
effect in a variety of cancers and it has been employed for the development of potent oncolytic
virotherapy agents for pancreatic cancer. Our ultimate goal is to develop an oncolytic adenovirus
enabling the treatment of patients with advanced or spread diseases by systemic injection. Systemic
application of oncolytic therapy mandates more efficient and selective gene delivery and needs to
embody sufficient antitumor effect even with limited initial delivery to the tumor location. In this review,
the current status of oncolytic adenoviruses from the viewpoints of vector design and potential
strategies to overcome current obstacles for its clinical application will be described. We will also
discuss the efforts to improve the antitumor activity of oncolytic adenovirus, in in vivo animal models,
and the combination therapy of oncolytic adenovirus with radiation and chemotherapy.