Gene therapy and cancer

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. 

Although many of the results generated to date provide hope for the future, gene therapy thus far has failed to provide a definitive cure for cancer. The lack of success is likely due to a number of factors, including  

Modifying lymphocytes in order to enhance their anti-tumour activity Modifying tumour cells to enhance their immunogenicity Inserting tumour suppressor genes into tumour cells 

Inserting toxin genes in tumour cells in order to promote tumour cell destruction Inserting suicide genes into tumour cells 

CH14 NUCLEIC-ACID- AND CELL-BASED THERAPEUTICS 

Breast cancer Malignant melanoma Ovarian cancer Small-cell lung cancer 

Colorectal cancer Tumours of the CNS Renal cell carcinoma Non-small-cell lung cancer 

An alternative anti-cancer strategy entails insertion of a copy of a tumour suppressor gene into cancer cells. For example, a deficiency 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 into p53-deficient tumour cells induces the death of such cells. A weakness of such an approach, however, is that 100% of the transformed cells would have to be successfully treated to fully cure the cancer. 

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Exhibit 11.13 FDA s Oversight on Gene Therapy and Cancer Vacdne... 

Jere D, Arote R, Cho MH, Cho CS, Biodegradable poly (/3-amino ester) derivatives for gene and siRNA delivery. In Gustafasson WB (ed.). New Gene Therapy and Cancer Research, Nova Science Publishers Inc., pp. 249-278. 

Chitosan Nanoparticles for Drug Delivery, Gene Therapy and Cancer Therapy. .. 289... 

As gene therapy and stem cell research progress, we can expect more regulatory requirements to be developed to ensure proper safeguards are implemented. Similarly, xenotransplantation and control of biopharmaceutical products will experience specihe regulatory controls as new advances are made. Exhibit 11.13 presents the FDA s current oversight on gene therapy and its cautious approach to cancer vaccine. 

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Schlag and Ulrike Stein, 2007 Gene Therapy for Cancer, edited by Kelly K. Hunt, Stephan A. Vorburger, and Stephen G. Swisher, 2007... 

This review discusses the gene-therapy-causes-cancer risk, and analyzes the risk/benefit factors for using gene therapy. 

Galanis E, Vile R, Russell SJ. 2001. Delivery systems intended for in vivo gene therapy of cancer Targeting and replication competent viral vectors. Crit Rev Oncol Hematol. 38 177-192. 

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Rakhmilevich, A.L., Janssen, K., Turner, J., Culp, J. and Yang, N.-S. (1997) Cytokine gene therapy of cancer using gene gun technology Superior antitumor activity of IL-12. Hum. Gene Then, 8, 1303-1311. 

Roth, J.A. and Cristiano, R.J. (1997) Gene therapy for cancer what have we done and where are we going J. Natl. Cancer Inst., 89,21-39. 

The pharmacokinetics of a gene drug within tumor tissue is a very important issue because cancer becomes one of the major targets for gene therapy, and various protocols are now under clinical trials (Roth and Cristiano, 1997). For in vivo gene delivery protocols, a gene drug, free or complexed with vector, is sometimes... 

Tahara, H. and Lotze, M.T. (1995) Antitumor effects of interleukin-12 (IL-12) applications for the immunotherapy and gene therapy of cancer. Gene Then, 2, 96-106. 

Such a catabolic reaction is indeed excluded in 6 alkyl purine derivatives. The parent compound of this group, 6-methylpurine, is known for its cytotoxicity its libera tion from the 2 -deoxyribonucleoside by purine nucleo side phosphorylases is used for detection of mycoplasma in cell cultures.19 It is highly potent and toxic to nonproliferating and proliferating tumor cells. Recently, the use of cytotoxic bases liberated by purine nucleoside phosphorylases such as 6-methylpurine was proposed as a novel principle in the gene therapy of cancer.20... 

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