Cancer is the commonest cause of death in Australia in the 21st century, and more than one-fifth of all cancers globally are due to chronic infection.
Current Laboratory Members
Professor Ian Frazer: Dr Graham Leggatt, Dr James Pang, Dr Purnima Bhat, Dr Stephen Mattarollo, Dr Sunny Liu, Mrs Allison Choyce, Ms Michelle Yong, Mr Sean Smith, Ms Nor Malia Abd Warif, Mr Azad Rahimpour, Mr Sam Fiorenza and Ms Dora Chan.
The Immunotherapy Group aims to develop new therapies for cancer and for chronic viral infection, targeting cells presenting tumour- or virus-specific antigens with antigen-specific T cells developed through immunisation.
Current Research Projects
Testing immunotherapy
We have continued over the last year to use a preclinical model for testing the requirements for effective immunotherapy for skin cancers, including cervical cancer, in which antigens of a particular virus (human papillomavirus) are expressed. The model involves grafting of skin transgenic for target antigens of interest to naïve recipients. In 2008, we tested the importance of different components of the inflammatory response in overcoming the natural resistance of skin cells to killing by the effector T cells induced by immunisation. These results suggested that a major non-structural protein of papillomavirus is able to reduce the susceptibility of skin cells to killing, suggesting an explanation for the ineffectiveness of papillomavirus-specific immunotherapy in the control of persisting papillomavirus infection and consequent cancer development.
Peripheral Tolerance
Animals expressing antigen in skin cells acquire tolerance to that antigen, an important observation as this problem is also seen in patients with epithelial cancer. Dr Graham Leggatt, along with student Sharmal Narayan, demonstrated that this tolerance was at least in part due to generation of antigen-specific CD25+ regulatory T cells. This observation suggests that immunotherapy targeted at inhibiting these cells may be necessary for control of antigen-bearing tumours by immunotherapy.
Immunotherapy in an antigen-experienced host
Prior exposure to antigen reduces the ability of animals and humans to respond to immunotherapeutic interventions. We have previously shown that this requires IL-10-secreting CD4 T cells. Over the last year we have determined that the IL-10 acts on other CD4 T cells to prevent generation of CD8 cells, and that this process is amplified by IFNγ secreted by the CD4 cells. We plan to take this finding to the clinic in 2010.
Imaging immune responses in vivo
In collaboration with The University of Queensland’s Centre for Microscopy and Microanalysis, we have been exploring new ways to track immune cells in the body after their induction by immunotherapy. Using high intensity magnetic fields, the sensitivity of magnetic resonance imaging can be increased to the point where individual cells can be tracked throughout the living animal over time. This technology should allow new insights into the trafficking of immune effector cells to their target tissues.
Needle-free skin antigen delivery
In collaboration with Professor Mark Kendall’s group at The University of Queensland’s Australian Institute for Bioengineering and Nanotechnology we have been examining the consequences of delivering antigen to skin using nanoneedles designed to penetrate only into the epidermis. Unexpectedly, the placement of such needles, with or without antigen, promotes rapid disappearance of Langerhans cells (a type of professional antigen presenting cell) from the skin. The fate of these cells and their ability to present antigen is now under study.
Clinical trials
Two major clinical trials initiated by our Group were completed in 2009, both conducted in conjunction with collaborators in Australia (Brisbane and Sydney) and in China (Wenzhou). A randomised placebo-controlled trial of efficacy of immunotherapy for genital warts initiated in 2006 recruited over 400 patients. An open label trial of immunotherapy for recurrent respiratory papillomatosis, a rare but serious papillomavirus-related childhood disease, showed promising results in the first (dose ranging) stage of the study, and we have now progressed the work to the second (efficacy evaluation) stage.
Professor Frazer is currently offering postgraduate projects in his laboratory. Click here for more information.