1. ¹Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
2. ²Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
3. ³Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

Correspondence: Dr X Zhang, Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Alkek Building N1010, Houston, TX 77030, USA. E-mail: xzhang@bcm.tmc.edu

Received 23 August 2006; Revised 3 April 2007; Accepted 8 April 2007; Published online 31 May 2007.

Abstract

The N-terminus of the ICP10 gene of type 2 herpes simplex virus (HSV-2) encodes a serine/threonine protein kinase (PK) domain that facilitates HSV-2 replication by activating the Ras/MEK/MAPK mitogenic pathway and suppressing apoptosis. We recently demonstrated that deletion of this oncogenic PK domain converts it to a potent oncolytic agent. This mutant, which we have designated FusOn-H2, preferentially replicates in and thus lyses tumor cells in which the Ras signaling pathway is constitutively activated. Here we show that FusOn-H2 exerts strong ability in inducing apoptosis in different lines of human tumor cells and in esophageal tumors growing in mice. The apoptotic effect produced by FusOn-H2 was not restricted to infected cells but extended to uninfected bystander cells, thereby increasing the lethality of the virus. These results add a novel killing mechanism to those previously assigned to FusOn-H2, rendering it an attractive candidate for clinical trials.