Baculoviruses as gene therapy vectors for human prostate cancer

Prostate cancer is the most commonly diagnosed cancer in ageing men in the western world. While the primary cancers can be treated with androgen ablation, radiotherapy and surgery, recurrent castration resistant cancers have an extremely poor prognosis, hence promoting research that could lead to a better treatment. Targeted therapeutic gene therapy may provide an attractive option for these patients. By exploiting the natural ability of viruses to target and transfer their genes into cancer cells, either naturally or after genetic manipulation, new generations of biological control can be developed. In this review we present the advantages and practicalities of using baculovirus as a vector for prostate cancer gene therapy and provide evidence for the potential of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) as a safer alternative vehicle for targeting cancer cells. Strategies to target baculovirus binding specifically to prostate cell surfaces are also presented. The large insertion capacity of baculoviruses also permits restricted, prostate-specific gene expression of therapeutic genes by cloning extended human transcriptional control sequences into the baculovirus genome.

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► Preferential Bv adhesion to cancer cells can be achieved by insertion of peptide ligands into the GP64 gene.
► Prostate specific therapeutic gene expression can be achieved with synthetic ‘human’ promoters inserted into Bv vectors.
► Bv vectors penetrate efficiently into complex human tissues.
► Retargeting of Bv to infect human cells reduces the production yield in insect cells by only 2-fold.