In this multidisciplinary research proposal we aim to develop a new therapeutic platform for hepatocellular carcinoma (HCC). HCC is the third leading cause of cancer death worldwide with a death rate greater than 600,000 persons annually. Currently the main curative treatments include resection, liver transplantation, or percutaneous local ablative treatment. However, all these approaches are primarily suitable for asymptomatic patients with very early and early HCCs. Transarterial chemoembolization (TACE) is the primarily indicated treatment for HCC. New evidence suggests that TACE with doxorubicin-eluting beads is superior to conventional TACE, in terms of reduced adverse event rates and improved survival. These beads are impregnated with doxorubicin, which is slowly released after being infused into the tumour vessels allowing a delivery of high intratumoral concentrations with a low serum doxorubicin level. Ideally, the injected chemotherapeutic should be retained in the tumor and be gradually released to avoid systemic toxicity. However, its selective injection is associated to significant passage into the systemic circulation. To improve drug delivery to the liver, the project “MicroEncapsDelivery” aims to develop a new therapeutic platform for the treatment of HCC that will deliver locally at the tumour the angiogenesis inhibitor hemopexin-like protein (PEX) and the immunostimulatory cytokine interleukin 12 (IL-12). This interdisciplinary therapeutic approach encompasses microencapsulation of genetically modified bone marrow derived mesenchymal stem cells, within biocompatible alginate beads, for the continuous and localised delivery of the therapeutic factors. Our goal is to develop the cell microcapsules and optimise and characterise the pharmacological profiles of PEX and IL-12 in vitro and their biodistribution in vivo in an established HCC rabbit animal model. The result will be dramatically reduced tumour in a manner that was unachievable until now.
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