Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963.

ABSTRACT: Replication-selective oncolytic viruses (virotherapeutics) are being developed as novel cancer therapies with unique mechanisms of action, but limitations in i.v. delivery to tumors and systemic efficacy have highlighted the need for improved agents for this therapeutic class to realize its potential. Here we describe the rational, stepwise design and evaluation of a systemically effective virotherapeutic (JX-963). We first identified a highly potent poxvirus strain that also trafficked efficiently to human tumors after i.v. administration. This strain was then engineered to target cancer cells with activation of the transcription factor E2F and the EGFR pathway by deletion of the thymidine kinase and vaccinia growth factor genes. For induction of tumor-specific cytotoxic T lymphocytes, we

SUBMITTER: Thorne SH 

PROVIDER: S-EPMC2040321 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature