The objective of this paper was to review a new category of gene therapy using oncolytic viruses for the treatment of
pancreatic cancer. The eligibility and feasibility of
oncolytic virus therapy as a novel therapeutic agent against
pancreatic cancer are discussed as well as basic research for clinical trials, including a historical perspective and the current status of these novel agents. Even combination
therapy, such as surgery with radiation and
chemotherapy, has not significantly improved the survival rate of
pancreatic cancer. Recently, a clinical trial (phase I and II) using an oncolytic adenovirus,
ONYX-015, was completed in patients with
pancreatic cancer. The phase II trial yielded beneficial results (
tumor reduction or stabilization) in about 50% of the patients. A phase I study of the efficacy of oncolytic herpes viruses, G207, OncoVEX
GM-CSF, and 1716 against a variety of
tumors has been completed, and G207 is in phase II trials for use against
brain tumors. In addition, a phase I trial using the herpesvirus showed good tolerance at all dosages. We discuss the basic scientific principles and current results of the above clinical trials with respect to these oncolytic viruses, and then compare the relative advantages and disadvantages of adenoviruses and herpesviruses as oncolytic agents. We also review the published literature on newly developed oncolytic viruses. The concept of oncolytic
therapy has been studied for a century. Recent technological developments have made these oncolytic viruses more
tumor-specific by exploiting the
tumor cell environments. In addition, these viruses have been reported to increase the immunosusceptibility of the
tumor cells, and have been designed to express other genes to increase the susceptibility of
tumor cells to other therapeutic agents.
Oncolytic virus therapy certainly appears to be a feasible treatment for
pancreatic cancer.