The chemotherapeutic ifosfamide is activated in the liver by cytochrome P450 (P450) enzymes and must travel systemically to the tumour site. The greater the distance of the tumour from the liver the greater the dose requirement for effective delivery. The toxicities induced by an effective dose for pancreatic cancer are too great. Activated ifosfamide can however be targeted to the pancreatic cancer reducing the dose requirement.
A new technology for encapsulating (figure 1) cells in polymers of cellulose sulphate has been developed . This technology protects the enclosed cells from the immune system but allows the free flow of soluble proteins and chemicals. Clinical studies have shown that it is possible to encapsulate 293 cells overexpressing P450 and deliver the capsules to the pancreas via the blood vessels without adverse effects. Lower doses of ifosfamide can then be systemically delivered and yet have a high active local concentration at the pancreas. A phase II trial is planned to confirm effectiveness in pancreatic cancer patients refractory to gemcitabine and abraxane or FOLFIRINOX .
|Figure 1: Capsules. Credit: Vinod Velayudhan. No changes were made. Creative Commons Attribution 2.0 Generic (CC BY 2.0).|
- Gunzburg, W. H., and Brian Salmons. ‘Use of Cell Therapy as a Means of Targeting Chemotherapy to Inoperable Pancreatic Cancer’. ACTA BIOCHIMICA POLONICA-ENGLISH EDITION- 52, no. 3 (2005): 601. https://www.researchgate.net/profile/Brian_Salmons/publication/236627164_Cell_and_gene_therapy_to_improve_cancer_treatment/links/0deec52d89a7e213a2000000.pdf.
- ‘PharmaCyte Biotech Issues Update on Preparations for Its Pancreatic Cancer Clinical Trial Other OTC:PMCB’. Accessed 10 March 2016. https://globenewswire.com/news-release/2016/02/22/812825/0/en/PharmaCyte-Biotech-Issues-Update-on-Preparations-for-Its-Pancreatic-Cancer-Clinical-Trial.html.