Project: DNA-targeted photoimmunotherapy for cutaneous T-cell lymphoma
This project is based in the Alfred Medical Research Precinct, Alfred Centre, Prahran
The overall aim of this research area is to develop a platform technology for receptor-targeted isotope radiotherapy / diagnostic imaging and for UVA phototherapy. For the UVA phototherapy component of the project, we have developed, UVASens, an ultraviolet light (UV) photosensitiser, which is ~1000 times more potent than compounds used clinically for the treatment of cutaneous T-cell lymphoma.
Our approach involves the use of a DNA minor groove binding ligand to target the radioisotope (radiotherapy / imaging) or iodine atom (phototherapy) to DNA. The DNA binding ligands used for these projects are based on the structure of Hoechst 33342, a well known DNA stain.
The aim of this project is to develop appropriate vehicles for the delivery of the DNA ligand to specific target cells. This will be performed by encapsulation in antibody-coated nanoparticles. Given the safety concerns with the use of radioisotopes, unlabelled DNA ligands will be used for the initial proof-of-concept experiments in this project. In this context the fact that these DNA ligands are intrinsically fluorescent is an advantage. It will enable the determination of the efficiency of targeting by fluorescence microscopy / flow cytometry (fluorescence yield of DNA bound ligand increases by ~30-fold).
The project will involve preparing the antibody-coated nanoparticle-based formulations and targeting specific receptors on cancer cells. Receptor systems that will be evaluated will be the IL-2 antigen and malignant MyLa cells overexpressing the receptor, and epidermal growth factor receptors and A431 cells. Evaluation of the efficacy of the constructs will involve flow cytometry (FACS), cell viability and apoptosis assays.
The Karagiannis group aims to understand the role of dietary antioxidants and chromatin modifying compounds on the genome and epigenome in health and disease. They develop predictive models of wound severity and potential for repair in the context of diabetic foot ulcers. This research direction also involves the development of new potential therapeutics.