Cancer-based gene therapy

An alternative anti-cancer strategy entails insertion of a copy of a tumour suppresser gene into cancer cells. For example, a dehciency in one such gene product, p53, has been directly implicated in the development of various human cancers. It has been shown in vitro that insertion of a p53 gene in some p53-dehcient tumour cell lines induces the death of such cells. A potential weakness of such an approach, however, is that 100 per cent of the transformed cells would have to be successfully treated to fully cure the cancer. Tumour suppressor-based gene therapy in combination with conventional approaches (chemotherapy or radiotherapy) may, therefore, prove most efficacious, and the sole gene-therapy-based medicine approved to date (in China only) is based upon this approach (Box 14.2). 

Gene therapy offers another potential avenue to fix the defective gene. The therapy itself is by no means straightforward. In a French gene therapy trial, three boys with SCID were treated using retrovirus-based gene therapy. They later developed cancer and one died of leukemia. Reviews showed that the retrovirus inserted near oncogenes and promoted development of cancer. 

S. Chada, R. Ramesh, A. M. Mhashilkar (2003). Cytokine- and chemokine-based gene therapy for cancer. Curr. Op. Mol. Ther. 5 463 74. 

Various protocols have been used to treat cancer by gene therapy using adenoviruses, which include gene-based immunotherapy, prodrug therapy and gene replacement approaches. These procedures are often employed in combination with... 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

An additional consideration that may influence the protocol used is the desired duration of subsequent expression of the gene product. In most cases of genetic disease, long-term expression of the inserted gene would be required. In other instances (e.g. some forms of cancer therapy or the use of gene therapy to deliver a DNA-based vaccine), short-term expression of the gene introduced would be sufficient/desirable. 

IMMUNE-BASED CANCER GENE THERAPY STRATEGIES... 

Anwer, K., C. Meaney, G. Kao, N. Hussain, R. Shelvin, R.M. Earls, R Leonard, A. Quezada, A.P. Rolland, and S.M. Sullivan, Cationic lipid-based delivery system for systemic cancer gene therapy. Cancer Gene Ther, 2000. 7(8) 1156-64. 

Zarif L, Mannino RJ. Cochleates lipid-based vehicles for gene delivery-concept, achievements and future development. In Kluwer H, ed. Cancer Gene Therapy Past Achievements and Future Challenges. New York Academic/Plenum Publishers, 2000 83. 

Kaplan JM. 2005. Adenovirus based cancer gene therapy. Curr Gene Ther. 5 595-605. 

Ramqvist T, Andreasson K, Dalianis T. 2007. Vaccination, immune and gene therapy based on virus-like particles against viral infection and cancer. Exp Opin Biol Ther 7 997-1007. 

Rein DT, Breidenbach M, Curiel DT. 2006. Current developments in adenovirus based cancer gene therapy. Future Oncol. 2 137-143. 

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