Updated on 9 August 2012
New hope for cancer: Suicide genes and encapsulated cells
Great strides have been made in the treatment of various cancers over the last decades. However, many forms of the disease are still only manageable rather than curable. These unmet medical needs include pancreatic cancer, hepatocellular carcinoma, glioma/ or glioblastoma and ovarian cancer. Novel treatment options include the use of "suicide genes" encoding enzymes that convert inactive pro-drugs into tumor toxic metabolites, also more popularly known as "gene directed enzyme pro-drug therapy" or GDEPT .
A number of such suicide genes and pro-drugs can be used for cancer therapy. Many have been tested in preclinical animal models and at least three, including herpes simplex virus thymidine kinase (HSV-tk), cytosine deaminase (CD) and cytochrome P450, have been tested in clinical trials in patients . A major drawback to GDEPT has been the relatively poor levels of gene transfer and/or short -term expression and a possible loss of the suicide gene in part due to the use of virus vectors for their delivery.
An alternative means of utiliszing the pro-drug activation strategy to treat tumours has been pioneered by the founders of Austrianova Singapore/SG Austria and involves the expression of the suicide gene from genetically modified cells, which are implanted near to the tumour (see Figure). These cells are protected from the patient's immune system by a bead structure, which also allows them to be physically confined to the site where they are needed. Another advantage of the use of encapsulated cells for the treatment of cancers is that the pro-drug can be activated in a sustained manner .
Encapsulation of living cells in beads and their subsequent implantation into patients was pioneered 30 years ago. One of the first materials used to encapsulate cells was alginate, a seaweed derived substance that is still in use today, mainly for the encapsulation of islet cells to treat diabetes, but alginate suffers from a number of drawbacks, including difficulties in sourcing at reproducible quality; limited stability; difficulties in setting up large-scale GMP production; difficulties in storing alginate encapsulated cells frozen; and often causing inflammatory/ or immune responses once implanted into patients. A good alternative encapsulation material is cellulose sulphate whichthat has been developed by the founders of Austrianova Singapore /SG Austria.
Capsules made of sodium cellulose sulphate offer a number of advantages, including reproducible production of the starting material, greater robustness of the capsules (permitting delivery by needles or catheters without bursting), good biocompatibility, both for the cells in the microcapsule as well as with the surrounding tissue upon implantation, and lack of immune or inflammatory responses. Moreover, large-scale GMP manufacturing of a cellulose sulphate encapsulated cell medicinal product for the treatment of pancreatic cancer has been shown to be feasible and acceptable to regulatory authorities .