| Popis: |
Recombinant adenoviruses are now used extensively in experimental protocols for the treatment of infectious, genetic and neoplastic disease. Adenovirus has emerged as of one the leading gene therapy vectors primarily because of its unrivalled capacity to deliver a transgene efficiently to a high proportion of target cells in vitro, ex vivo and in vivo. Most published studies use a standard first generation replication-deficient Ad vector with high level transgene expression being driven by a strong constitutive promoter. However, considerable research effort is now going into optimizing vectors for specific clinical applications. The virus particle is being manipulated so that it can be re-targeted to infect specific cell types. Tumor-specific promoters are also being exploited to restrict expression to malignant cells. Furthermore, the safety and performance of adenovirus vector systems are being enhanced by the deletion of additional essential genes from the vector backbone and the development of promoters that can be actively regulated in vivo. A plethora of different therapies are being explored for cancer gene therapy using adenovirus vector systems and they are reviewed extensively within this chapter. The results of pre-clinical studies have been highly encouraging and already data from a series of human phase I clinical trials have been published. Most early studies naturally concentrated on assessing the effect of a single therapeutic agent including immunization with tumor specific antigens, cytokines, tumor suppressors, ribozymes/antisense technology, prodrug technology and suppressors of tumor angiogenesis. The complexity of the field is increasing rapidly with an increasing number of studies exploring the potential additive or synergistic benefits of combining multiple transgenes. Ad vectors will readily accommodate multiple gene delivery to a target cell population either using a single or multiple vectors. |
