1. ¹Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
2. ²Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
3. ³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

Correspondence: Xiaoliu Zhang, Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Fax: (713) 798-1230. E-mail: xzhang@bcm.tmc.edu

Received 29 January 2004; Accepted 27 February 2004.

Abstract

In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8⁺ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses.