Targeting Strategies in Cancer

We have identified a series of molecules selectively expressed on cancer cells, and in the tumour microenvironment, that can be targeted for cancer therapy. This includes conformationally exposed receptor epitopes, such as found on the Epidermal Growth Factor Receptor (EGFR) and which led to the development of mAb806 and our first-in-human trials of this molecule. Our research findings have provided a new paradigm in antibody-based targeting and therapy of solid tumours. This work has expanded to incorporate structure-function studies of additional novel antibodies we have developed that target cell surface receptors and tumour microenvironment in tumours, as well as investigating mechanisms of resistance to antibody therapeutics, and targeting key molecules involved in sustaining the tumour microenvironment.

Antibody Engineering

We have developed techniques for generation and humanisation of antibodies. Recent molecular engineering, structural and modelling approaches in our laboratory have defined novel Fc:FcRn and Fc:FcγR interactions, which result in improved immune effector function and bioavailability of humanised antibodies. We have also developed strategies to deliver payloads specifically to tumours through conjugation of drugs, toxins and isotopes to recombinant antibodies, peptides and nanoparticles, both in preclinical models and more recently in clinical trials in cancer patients. These studies are showing encouraging results in patients with cancers of the brain, colon and breast, as well as other solid tumours.

Tumour Payload Delivery

The development of recombinant antibodies for cancer therapy has emerged as one of the most promising areas in oncology therapeutics, both as single agents, and for payload delivery. The concept of being able to deliver toxins through antibody-drug conjugates, or radiotherapy by antibody-radioisotope conjugates targeting the payload to sites of disease, are exciting and promising approaches that we are exploring preclinically and clinically with antibodies developed in our laboratory.

Novel Metabolic Tracers

An exciting recent development in the molecular imaging of cancer comes from the identification of critical biochemical pathways responsible for tumour growth and metastasis, and immune targets which can be exploited for therapy, which can be imaged with novel SPECT and positron emission tomography (PET) tracers. Taking the discovery of novel metabolic tracers in the laboratory to clinical trials is a major focus of our molecular imaging / PET research program and is leading to a deeper understanding of tumour biology and therapy response.