About the Project
This is a project which aims to investigate how tumours and normal tissue internalise drugs such as cancer therapy antibodies in real in vivo models and in patients. My laboratory has recently shown that changing this internalisation can alter therapy mechansims. The uptake of drugs by both target cells and normal cells in humans, a process called endocytosis, is critical for many medicines including antibody therapies, nano-medicines and antibody-drug conjugates (ADCs). Our understanding of cellular uptake mechanisms has developed significantly in the last 5 years. However, these advances in cell biology have not fully translated to the drug delivery, design and immunological fields. The role of endocytosis is also important for naturally occurring nanoparticles, such as viruses and exosomes and CAR-T therapy has been shown to be antigen clustering dependent, An example of this is the recent advance in cancer therapy using anti-PDL1 and anti PD-1 antibodies, known as checkpoint inhibitors. Recent data has shown that in cases of poor outcome the pharmacokinetic properties of anti-PDL1 antibody is an issue, with tumour degradation of the antibody occurring very quickly. Another example is the drive to understand CoV-virus entry into human cells to inform to inform potential anti-viral therapies. Findings from our program may be applied to multiple clinical settings (e.g. antibody therapy in multiple sclerosis or anti-HIV antibody therapy). This project crosses the fields of cell biology, immunology, cancer, drug targeting and clinical trials. Techniques include (but are not limited to) imaging, electron microscopy, fluorescence activated cell sorting and in vivo work in murine models and patient samples.
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