Cancer Gene Therapy Strategies

IMMUNE-BASED CANCER GENE THERAPY STRATEGIES 

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IMMUNE-BASED CANCER GENE THERAPY STRATEGIES... 

Crystal, R.G. (1999) In vivo and ex vivo gene therapy strategies to treat tumors using adenovirus gene transfer vectors. Cancer Chemother. Pharmacol., 43, S90-S99. 

Hamstra, D. A., and Rehemtulla, A. Toward an enzyme/prodrug strategy for cancer gene therapy Endogenous activation of carboxypeptidase A mutants by PACE/furin family of propeptidases. Hum. Gene Ther. 10 235-248, 1999. 

Numerous transcriptionally targeted replication-competent adenovimses and herpes viruses have been shown to be highly specific (up to 10,000-fold relative to nontarget cells) in cell culture experiments. In addition, animal models have demonstrated their safety and efficacy. It thus appears that the transcriptional targeting of viral replication holds some promise as a strategy for cancer gene therapy. 

Gene therapy provides a significant opportunity to devise novel strategies for the control or cure of cancer. Several approaches of cancer gene therapy are currently being investigated ... 

Bettinger T, Read ML. Recent developments in RNA-based strategies for cancer gene therapy. Curr Opin Mol Ther, 2001, 3(2), 116-24. 

Most cancer gene therapy studies have up until now used viral vectors, in particular ADV, to deliver the therapeutic DNA into the tumor cells. Many clever ways have been devised, and numerous cellular processes have been explored as targets for enhancing killing of cancer cells in vitro, for example by increasing apoptosis, and many times these strategies have also shown efficacy in animal tumor models. Herein, only the most significant studies and concepts will be discussed. 

Freytag SO, Kim JH, Brown SL, Barton K, Lu M, Chung M (2004) Gene therapy strategies to improve the effectiveness of cancer radiotherapy. Expert Opin Biol Ther 4 1757-1770... 

To date, the majority of gene therapy trials undertaken aim to cure not inherited genetic defects, but cancer. The average annual incidence of cancer reported in the USA alone stands at approximately 1.4 million cases. Survival rates attained by pursuit of conventional therapeutic strategies (surgery, chemo/radiotherapy) stand at about 50 per cent. 

Table 14.5 Some therapeutic strategies being pursued in an attempt to treat cancer using a gene therapy approach. Refer to text for details...

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). 

The large number and types of gene therapy trials for cancers reflect both the potential opportunities to develop treatments and the fact that a single strategy will not likely work for aU forms of cancer. 

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