Oncolytic viral therapy for human cancer: Challenges revisited

• Published in: Drug development research 2005-12, Vol.66 (4), p.260-277
• Main Author: Tong, Alex W.
• Format: Article
• Language: English
• Subjects: Adenovirus; Biological and medical sciences; cancer; chemotherapy enhancement; Medical sciences; oncolytic virus; Pharmacology. Drug treatments; RGD; siRNA; transgene
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.20058

Conditional replicative, oncolytic adenoviruses are genetically modified to replicate primarily in malignant cells with oncogenetic defects, selectively killing cancer cells in the process. Viral progenies released within the tumor microenvironment can penetrate, infect, and destroy additional cell layers of the solid tumor mass. Much excitement has been generated over the clinical successes of ONYX‐015 adenovirus treatment for advanced head and neck cancer, pancreatic carcinoma, and metastatic colorectal carcinoma at the locoregional level. However, follow‐up trials with systemic viral administration have not met initial expectations. This review examines recent basic science developments that may potentially overcome the two key limitations of systemic virotherapy, namely, suboptimal tumor oncolysis and pharmacokinetic shortcomings due to rapid viral clearance. Late‐generation constructs incorporate alternative viral backbone modifications and antitumor transgenes to enhance oncolytic potency. Furthermore, altered viral tropism, through masking or substitution of viral surface components, is likely to promote tumor‐selective targeting and safety. Merits of these approaches in the clinical arena are discussed. Drug Dev. Res. 66:260–277, 2006. © 2006 Wiley‐Liss, Inc.