Identification and characterization of alphavirus M1 as a selective oncolytic virus targeting ZAP-defective human cancers
Abstract
Although oncolytic virotherapy is showing great promise in clinical trials, not all patients are benefiting. Identifying predictors of therapeutic effectiveness for each oncolytic virus would provide a good chance to increase response rate. Here, we describe an alphavirus (M1) that possesses selective and potent antitumor activity through intravenous infusion, whereas its replication is controlled by the zinc-finger antiviral protein (ZAP) gene. A survey of cancer tissue banks reveals that ZAP is commonly deficient in human cancers, suggesting extensive application prospects of M1. Our work provides an example of a potentially personalized cancer therapy using a targeted oncolytic virus that can be selectively administered to patients with ZAP-deficient tumors. We predict that such agents will form the armamentarium of cancer therapy in the future.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- October 2014
- DOI:
- 10.1073/pnas.1408759111
- Bibcode:
- 2014PNAS..111E4504L