Although differential expression of ribonucleotide reductase between liver metastases and normal liver serves to drive differential replication of HSV-1 mutants that are defective in viral ribonucleotide reductase, we are testing the hypothesis that tumor associated promoters (e.g. CEA, muc1) can regulate immediate-viral gene expression in HSV-1 to limit viral replication (and oncolysis) specifically to tumor cells. Herpes simplex virus and adenovirus mutants whose life cycle is regulated by a tumor associated promoter have been constructed. The molecular regulation of their gene expression and replication, as well as their anti-neoplastic efficacy are currently under examination in vitro and in vivo.

Tumor Associated Promoters for Regulation of Viral Replication and Oncolysis
Principal Investigator: Kenneth K. Tanabe, MD
Group Members: Soundararajalu Chandrasekhar, PhD; James M. Donahue, MD; John T. Mullen, MD