Replication-selective oncolytic adenoviruses: virotherapy aimed at genetic targets in cancer.
Replication-selective oncolytic adenoviruses represent a novel cancer treatment platform. Clinical studies have demonstrated the safety and feasibility of the approach, including the delivery of adenovirus to tumors through the bloodstream (Heise et al., 1999b; Reid et al., 1999; Nemunaitis et al., 1999). The inherent ability of replication-competent adenoviruses to sensitize tumor cells to chemotherapy was a novel discovery that has led to chemosensitization strategies. These data will support the further development of adenoviral agents, including second-generation constructs containing exogenous therapeuitc genes to enhance both local and systemic antitumoral activity (Heise and Kirn, 2000; Hermiston, 2000; Agha-Mohammadi and Lotze, 2000). In addition to adenovirus, other viral species are being developed including herpesvirus, vaccinia, reovirus and measles virus (Kirn, 2000a; Martuza, 2000; Norman and Lee, 2000; Mastrangelo et al., 2000; Coffey et al., 1998; Martuza et al., 1991; Kirn, 2000b; Lattime et al., 1996). Since intratumoral spread also appears to be a substantial hurdle for viral agents, inherently motile agents such as bacteria may hold great promise for this field (Low et al., 1999; Sznol et al., 2000). Given the unknown predictive value of in vitro cell-based assays and murine tumor model systems for the efficacy and therapeutic index of replication-selective oncolytic adenoviruses in patients, we believe that encouraging adenoviral agents must be tested in well-designed clinical trials as soon as possible. Only then can the true therapeutic potential of these agents be realized.
Kirn
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Imperial Cancer Research Fund, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
D017500:Adenovirus E1A Proteins / Q000235:genetics; D017501:Adenovirus E1B Proteins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics* / Q000254:growth & development; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D005544:Forecasting; D015316:Genetic Therapy; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000628:therapy*; D014779:Virus Replication
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins