Adenoviral Vectors for Cancer Gene Therapy

Wenli      Zhao; Masanobu      Kobayashi; Masuo      Hosokawa; Prem      Seth

Abstract

Cancer gene therapy is considered a very viable approach for the treatment of cancer. The basic idea is to introduce the therapeutic gene, often in the form of a foreign cDNA, into the cancer or other appropriate target cells. For gene delivery purposes, several viral and non-viral vectors have been described. One vector that has become very popular for the purpose of cancer gene therapy is adenovirus. Main reasons are that the recombinant adenoviruses expressing the foreign therapeutic genes can be easily generated, and that the infection of the target cells with the recombinant adenoviruses produces large quantities of the therapeutic proteins. The review describes the basic characteristics and the molecular biology of adenoviruses. This review further describes various methods to generate the recombinant adenoviruses. These include the methods to generate the first generation adenoviruses (E1 deleted), up to the most recently used gutless viruses (with complete viral deletions). A critical compari son of the advantages and disadvantages of various methods is also described. The review also describes the use of adenoviruses which selectively replicate in cancer cells. The review further describes the various approaches for cancer gene therapy currently being exploited. These include the gene replacement strategies using tumor suppressor genes, anti-oncogenes, use of suicide genes, immunomodulation and anti-angiogenesis approaches. An in depth analysis of the pre-clinical data obtained using adenoviral vectors for these cancer gene therapy approaches is also described. The review concludes with a critical discussion of the adenoviruses for cancer gene therapy.

Keywords: adenovirus, adenoviral vector, cancer gene therapy, foreign cdna, viral vector

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