NY-ESO-1 has served as a model antigen for our laboratory and clinical research. This has involved preclinical and clinical evaluation in Phase I and Phase I/II studies that have characterized tumor antigen expression and immune responses in patients. We assess spontaneous and vaccine-induced immune responses against melanoma, and have a particular interest in developing methods for understanding functional subpopulations within melanoma and the optimal ways of targeting them therapeutically. Ongoing research involves the evaluation of immune checkpoint inhibition in collaboration with the Ludwig/CRI CVC trials network and the pharmaceutical industry.
Major challenges in the treatment of melanoma arise because of the tumour’s inherent plasticity, which enables escape variants to arise after treatment. This plasticity carries the hallmarks of epithelial to mesenchymal transition (EMT) and is the subject of intense research in our lab and worldwide. We use extensive genomic and gene-expression profiling techniques to identify molecules and molecular pathways that mediate the dynamic changes observed in vitro, and which are associated with different clinical outcomes in melanoma patients. These molecules are being evaluated as potential clinical targets.
Our collaborative relationships with pharmaceutical companies, including CSL Ltd, Bristol-Myers Squibb, Sirtex, Roche, Merck and GlaxoSmithKline, continue to provide basic and translational clinical research opportunities. Together with CSL we embarked on a collaborative project aiming to identify novel antibodies to target melanoma cells using phage display technology. We also have longstanding collaborations with GlaxoSmithKline to study inhibitors of the MAPK pathway in immune cells and melanoma, tumour antigens and predictive immune gene signatures.
Current clinical trials include combination of intrahepatic embolization and a radiosensitizer in patients with uveal melanoma and liver-only metastases, a phase I trial that evaluates a combination therapy of BCG with ipilimumab in Stage III/IV melanoma, and several landmark international trials including a phase II trial that evaluates combination immunotherapy with nivolumab & ipilimumab. We have an active non-interventional trial which examines self- reported quality of life changes for patients who receive immunotherapy outside of the rigid clinical trial environment. Upcoming interventional trials will examine immunotherapy in combination with other novel agents in an effort to improve both short- and long-term outcomes for patients.