Intraperitoneal delivery of hrR3 and ganciclovir prolongs survival in mice with disseminated pancreatic cancer

Background and Objectives Intraperitoneal dissemination of pancreatic cancer is associated with a poor prognosis. Surgical resection does not prolong survival. Here we describe a novel approach to this difficult clinical problem consisting of intraperitoneal delivery of the herpes simplex virus (HSV) vector (hrR3) to mice with peritoneal dissemination of the pancreatic cancer cells. Methods The human pancreatic cancer cell line (SW1990) was implanted into the abdominal cavity of nude mice. Fifteen days later, the abdominal neoplasm was treated by intraperitoneal injection of the replication‐conditional HSV vector (hrR3). The mutant lacks the ribonucleotide reductase gene, but contains an intact HSV‐tk gene. Beginning 5 days after vector injection, mice were treated with a 14‐day course of ganciclovir. Results Long‐term survival (150 days) was seen in 70% of mice receiving hrR3 and ganciclovir, 40% of mice receiving hrR3 alone, and 0% of untreated mice. No vector‐related mortality was observed. X‐Gal tissue staining revealed blue‐stained cells only in tumor nodules, not in normal organs. Conclusions Intraperitoneal delivery of hrR3 and ganciclovir improves survival in this murine model of peritoneal dissemination of pancreatic cancer. The ability of hrR3 to replicate only in rapidly dividing cells makes this virus an attractive vector for gene therapy of cancer. J. Surg. Oncol. 1999;72:136–141. © 1999 Wiley‐Liss, Inc.