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Oncolytic viral therapy for human cancer: Challenges revisited
Author(s) -
Tong Alex W.
Publication year - 2005
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20058
Subject(s) - oncolytic virus , virotherapy , cancer research , tropism , cancer , tissue tropism , medicine , clinical trial , tumor microenvironment , virology , virus , biology , immunology , tumor cells
Abstract 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.