Tumour-targeted drug delivery in cancer therapy
Tumour-targeted drug delivery is one of the most important areas in cancer research. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues thus improving the efficacy and reducing the side-effects. Engeneic delivery vehicles (EDVs) are bacterially-derived mini-cells. These mini-carriers can be loaded with active drugs or small interfering ribonucleic acid (siRNA) and targeted to tumour cells in vivo via bi-specific antibodies. A Phase I clinical trial has recently been completed that proved the safety of the EDV technology in humans. A Phase II study to prove the clinical benefits of EDV system is underway. CD14 project was designed as collaboration during Phase 1 trial to survey the scale of host immune response to the treatment with EDV. Peripheral blood mononuclear cells (PBMCs) are a critical component in the immune system to fight infection and adapt to intruders. It was found that EDVs do not affect viability, proliferative activity, or metabolic activity of human PBMC in vitro. However, EDVs are sensed by human PBMCs and induce a response similar to that of bacterial components such as lipopolysaccharides, lipoproteins or flagellin. They also induced tumour necrosis factor (TNF)-alpha and IFN-beta gene expression. Using inhibitor analysis, toll-like receptor 4 (TLR4) was implicated in stimulation of PBMC by EDVs. The CD14 project evaluated the interaction of EDVs with the human immune system in a highly relevant in vivo situation. Future collaboration will be very important for the next stage clinical trials to survey the response of immune system to EDVs in cancer patients.
