Interspecies adenovirus fiber shows 'evolutionary' advantage for oncolytic therapy of gliomas.

摘要

Oncolytic adenoviruses are a promising therapeutic strategy to treat malignant gliomas. After being tested in the 50s, virotherapy approaches were put on standby as cancer treatments. Safety and efficacy required improvement but neither the technology nor the knowledge were then available. During the revival of the field of virotherapy in the 90s, oncolytic adenoviruses were reinvented as tools to overcome the obstacle of viral vectors ("vector gap") that did not infect sufficient number of tumor cells in vivo. Two groups, one working with herpes viruses1 and the other working with replication competent adenoviruses,2 developed new strategies for tumor selective oncolytic viruses. The potent therapeutic effect predicted by the preclinical studies on the first oncolytic adenoviruses did not materialize in the clinical scenario. Thus, treatment of residual malignant brain tumors after treatment with an E1B-55K deleted adenovirus, termed ONYX 015, did not show significant anti-tumor effect, although its safety profile in human patients was almost impeccable.3 The lesson learned from this endeavor was that the delivery of replication competent adenoviruses to cancer cells is safe but requires improvement to increase their efficacy. One of the basic strategies to increase efficacy relies on improving the infectivity of the vector. Analyses of adenoviral receptors in brain tumors suggested that new vectors have to be designed to infect more efficiendy than wild type viruses. In this issue, Paul and colleagues report an elegant strategy to modify the adenoviral fiber and generate vectors that infect malignant gliomas with great efficacy.