Clinical trials of cancer treatment using encapsulated cells to target chemotherapy

Until date, two clinical trials of encapsulated cells, expressing the cytochrome P450 gene as a suicide gene, followed by administration of oxalophosphamide prodrug chemotherapeutic agents requiring activation by cytochrome P450, have demonstrated that the treatment to be is both safe and efficacious. The first trial was performed in humans with pancreatic cancer and the second trial was a study in dogs, companion pets that were brought to a veterinary clinic for treatment.

Trial 1) Phase I/II clinical trial in human patients with pancreatic cancer
In this clinical trial, performed in Germany and involving 14 patients, the encapsulated cells were delivered to vessels leading to the tumour using supra-selective catheteriszation of the tumour feeding blood vessels [2,4]. Upon release of the encapsulated cells from the catheter, they are propelled by the blood flow into evenr smaller vessels leading to the tumour where they become lodged.

The safety of this means of delivery of encapsulated cells was successfully demonstrated in advance of thea clinical trial in a porcine model. The clinical study additionally demonstrated the feasibility of specifically delivering the encapsulated cells to vessels leading to the pancreas/small intestine and no evidence of pancreatitis, foreign body reactions or circulatory disturbances.

Instillation of the encapsulated cells was followed by intra venous iv infusions of low doses of the oxalophosphamide, ifosfamide. The infused ifosfamide is carried by the blood stream into the beads housing the cytochrome P450 expressing cells, where it is catalysed to a relatively short-lived and tumour toxic metabolite, which is then released from the capsules and flows directly into the pancreas and tumour but selectively destroys only tumour cells.