Biomedical Engineering Reference
In-Depth Information
focus of attempts at corrective gene therapy. Cystic fi brosis is the most common inherited mono-
genetic disease in Europe and the USA, and sufferers have a typical life expectancy of less than
40 years. Over a third of the 100 or so gene therapy trials thus far undertaken to treat inherited
disorders have specifi cally targeted cystic fi brosis.
Several vectors have been used in an attempt to deliver the cystic fi brosis gene to the airway epi-
thelial cells of sufferers. The most notable systems include adenoviruses and cationic liposomes.
Vector delivery to the target cells can be achieved directly by aerosol technology. Delivery of
CFTR cDNA to airway epithelial cells (and subsequent gene expression) has been demonstrated
with the use of both vector types. However, in order to be of therapeutic benefi t, it is essential that
5-10 per cent of the target cell population receive and express the CFTR gene. This level of inte-
gration has not been achieved so far; and, furthermore, gene expression has often been transient.
14.5 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 approxi-
mately 1.4 million cases. Survival rates attained by pursuit of conventional therapeutic strategies
(surgery, chemo/radiotherapy) stand at about 50 per cent.
Initial gene therapy trials aimed at treating/curing cancer began in 1991. Various strategic ap-
proaches have since been developed in this regard (Table 14.5). Numerous trials aimed at assess-
ing the application of gene therapy for the treatment of a wide variety of cancer types are now
underway (Table 14.6).
Although many of the results generated to date provide hope for the future, gene therapy thus
far has failed to provide a defi nitive cure for cancer. The lack of success is likely due to a number
of factors, including:
•
A requirement for improved, more target-specifi c vector systems.
•
A requirement for a better understanding of how cancer cells evade the normal immune response.
•
For ethical reasons, most patients treated to date were suffering from advanced and widespread
terminal cancer (i.e. little/no hope of survival if treated using conventional therapies). Cancers
at earlier stages of development will probably prove to be more responsive to gene therapy.
Table 14.5
Some therapeutic strategies being pursued in an attempt to treat
cancer using a gene therapy approach. Refer to text for details
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
Inserting genes, such as a multiple drug resistance (
mrd
) gene, into stem cells to
protect them from chemotherapy-induced damaged
Counteracting the expression of oncogenes in tumour cells by inserting an
appropriate antisense gene
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