140904-jamesbraund-1302

Cancer immunobiology

Laboratory overview

Our laboratory focuses on understanding immune responses to cancer and developing ways to monitor patient responses to cancer immunotherapies as well as finding other ways to harness and improve this response. This has led to detailed studies of antigen expression in melanoma and to investigations of the poorly understood mechanisms of heterogeneity in this disease. This includes extensive studies of cellular sub-populations in melanoma.

Our clinical and laboratory team efforts are focused on three research streams:

  • Investigating immunity in cancer patients, with a focus on cancer antigens and identifying potential new targets for melanoma therapy;

  • Exploring the regulators of dendritic cell function, including antigen uptake, migration, cytokine secretion, antigen cross-presentation and T-cell stimulation;

  • Identifying and characterizing heterogeneity in metastatic melanoma, with focus on subpopulations of cells and plasticity.

Immunotherapy is revolutionising the way we’re treating some cancers and as the proof of the benefits increases, it’ll move to the front of the cancer treatment line. Prof. Jonathan Cebon. Head, Cancer Immunobiology Lab
study-at-ONJCRI 140404-jamesbraund- 1588 140904-jamesbraund-0984

Our focus

NY-ESO-1

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.

EMT

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.

Translational research

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.

Clinical trials

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.

 

Quick Facts

What is cancer immunobiology?

The scientific study of how cancer cells interact with the body's immune system. Researchers investigate molecular mechanisms that can be activated within the immune system to identify and destroy cancer cells.

What is cancer immunotherapy?

Immunotherapy is when the body's natural defence, the immune system, is 'switched' on to identify and destroy cancer cells. 

How does immunotherapy work?

Normally the immune system is activated when it's under attack. It will try to fight off pathogens, such as viruses or infection until the body is healthy again.  The healthy immune system will not attack the hosts own cells unless there is a signal that the cell is to be eliminated. Cancer cells can stealthily evade the control of the immune system, allowing growth to occur unabated.

Immunotherapy drugs contain antibodies that affect the way the immune system is activated allowing the immune system to identify and destroy cancer cells.

1.      Andrews, M.C., N. Turner, J. Boyd, A.W. Roberts, A. Grigg, A. Behren and J.S. Cebon. Cellular mechanisms underlying complete hematological response of chronic myeloid leukemia to BRAF/MEK inhibition in a patient with concomitant metastatic melanoma. Clin Cancer Res, 2015, Jul 22. pii: clincanres.0393.2015. [Epub ahead of print]

2.      Chang-Hao Tsao, S., J. Weiss, C. Hudson, C. Christophi, J. Cebon, A. Behren and A. Dobrovic. Monitoring response to therapy in melanoma by quantifying circulating tumour DNA with droplet digital PCR for BRAF and NRAS mutations. Sci Rep, 2015. 5: p. 11198.

3.      Parakh, S., C. Murphy, D. Lau, J.S. Cebon and M.C. Andrews.Response to MAPK pathway inhibitors in BRAF V600M-mutated metastatic melanoma. J Clin Pharm Ther, 2015. 40(1): p. 121-3.

4.      Prithviraj, P., M. Anaka, S.J. McKeown, M. Permezel, M. Walkiewicz, J. Cebon, A. Behren and A. Jayachandran. Pregnancy Associated Plasma Protein-A links pregnancy and melanoma progression by promoting cellular migration and invasion. Oncotarget, 2015. Jun 30;6(18):15953-65.

5.      Behren, A., M. Anaka, P.H. Lo, L.J. Vella, I.D. Davis, J. Catimel, T. Cardwell, C. Gedye, C. Hudson, R. Stan and J. Cebon. The Ludwig Institute for Cancer Research Melbourne Melanoma Cell Line Panel. Pigment Cell Melanoma Res, 2013. 26(4): p. 597-600.

For a complete list of Jonathan Cebon's publications, click here.

Study at ONJCRI

Learn more