The Experimental Therapeutics Laboratory is a collaborative venture of the Hanson Institute between scientists from the Sansom Institute for Health Research (University of South Australia) and the Cancer Clinical Trials Unit (Royal Adelaide Hospital Cancer Centre).
We perform basic, translational and clinical research that aims to improve cancer diagnosis and treatment, as well as exploring novel immunotherapeutic approaches to treat cancer and other diseases including chronic and acute infections. We are expert at exploiting the specificity and power of the immune system to help us design, develop, and implement cutting edge approaches to new diagnostics and therapeutic agents.
Our industry links, experience and our clinical expertise together ensure that our research has a strong likelihood of generating potentially commercialisable applications and improved therapeutic outcomes for patients.
Associate Professor John Hayball (UniSA)
Professor Michael Brown (Director Clinical Trials Unit, RAH; Adjunct Professor, UniSA)
Dr Paul Howley (Sementis Pty Ltd; Adjunct Senior Lecturer, UniSA)
Dr Kerrilyn Diener (NHMRC Early Career Research Fellow, UA; Adjunct Senior Lecturer, UniSA)
Dr Darren Miller (UniSA)
Dr Cara Fraser (RAH; Adjunct Lecturer, UniSA)
Dr Erin Lousberg (UA; Adjunct Lecturer, UniSA)
Dr Alex Staudacher (RAH)
Dr Liang Liu (UniSA)
Dr Tamara Cooper (UniSA)
Research support staff
Ms Helen Palthorpe (UniSA)
Ms Rosa Katsikeros (UniSA)
Ms Susan Christo (PhD student, UniSA)
Ms Natalie Stevens (PhD student, UniSA)
Ms Melissa Tan (Honours student, UniSA)
Ms Shamika Moore (Honours student, UA)
Ms Bianca Van Diermen (Honours student, UA)
List of Awards/Honours received by laboratory members (2010-2012)
Erin Lousberg (Postdoctoral Research Officer): Travel Scholarship to attend DC2010, International Society for Dendritic Cell and Vaccine Science (2010); HDR International Travel Scholarship to attend DC2010 (Sansom Institute, UniSA, 2010); Best Oral Presentation by a PhD Student at the Adelaide Immunology Retreat (AIR-6) (Australasian Society for Immunology, SA Branch, 2010)
Susan Christo (PhD Student): Australasian Society for Immunology SA/NT Annual Student Retreat 6 Prize for Most Outstanding Presentation by an Honours/Masters Student (2010); University of South Australia Honours Medal (2011); University of South Australia PhD Top Up Scholarship (2011-2013); Royal Adelaide Hospital DAWES Top Up Scholarship; Honours Scholarships for the Division of Health Sciences, UniSA (2010); UniSA High Achiever Summer Scholarship – Top Up (2010); Cancer Council SA Vacation Scholarship (2010)
Natalie Stevens (PhD student): PhD Scholarship – Australian Postgraduate Award (2012-2014); Royal Adelaide Hospital Research Committee Dawes Top-Up Scholarship (2012-2014); Royal Adelaide Hospital Research Committee Honours Scholarship (2011)
Bianca Van Diermen (Hons student): School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology Honours Scholarship, UA (2012)
Shamika Moore (Hons student): School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology Honours Scholarship, UA (2012)
Current Competitive Grants and Fellowships
ARC Linkage Project Grant LP120100606. 'The development of a potent new passive immunotherapeutic for the treatment and prevention of bacterial sepsis and septic shock'. JD Hayball, T Kuchel and M Chapman. Awarded $333,000 for 2012-14 (ARC and Industry Partners)
NHMRC Project Grant, Application ID 1020984. 'The consequences of innate immune inflammatory responses during early pregnancy and their effect on reproductive outcomes'. KR Diener. Awarded $326,175 for 2012-2014
NHMRC Training Fellowship, Application ID 1012386. ‘Innate anti-viral effector responses and adverse reproductive outcomes’. KR Diener. Awarded $290,032 for 2011-2014
NHMRC project grant 'CARPETS: A Phase I Open Label Study of the Safety and Immune effects of an Escalating Dose of Autologous GD2 Chimeric Antigen Receptor-Expressing Peripheral Blood T Cells in Patients with Metastatic BRAF-Mutant and GD2-Positive Melanoma'. MP Brown, I Lewis, CM Bollard, MK Brenner, JD Hayball. Awarded $338,459.60 for 2011-2013
NHMRC Project 'Chemokine gradients for directed migration of captured cells and guidance of tissue engineering'. HJ Griesser, RD Short, K Vasilev, MP Brown, JD Hayball, C McFarland. Awarded $680,000 for 2010-2012
RISS Ltd Researcher Access Program. 'CARPETS: A Phase I Open Label Study of the Safety and Immune effects of an Escalating Dose of Autologous GD2 Chimeric Antigen Receptor-Expressing Peripheral Blood T Cells in Patients with Metastatic BRAF-Mutant and GD2-Positive Melanoma'. MP Brown, I Lewis, CM Bollard, MK Brenner. Awarded $100,000 for 2011-2013.
CRC for Wound Management and Innovation. 'Novel bioactives for wound repair'. JD Hayball. Awarded $75,000 for 2011-13
Royal Adelaide Hospital Research Committee Mary Overton Early Career Research Fellowship. 'A comparative analysis of the relative therapeutic efficacy of phenotypically-distinct populations of genetically-modified tumour-specific T cells as detected and assessed by functionalised solid support surfaces'. KR Diener. Awarded $252,000 for 2011-2013. (Note: declined due to acceptance of NHMRC Training Fellowship)
Current research activities
Melanoma research projects:
The overall aim of these projects is to translate laboratory advances in melanoma research to improved clinical outcomes for patients with advanced melanoma. Some of the technologies being developed in non-melanoma projects in our laboratory may produce an original solution to the problem of detecting the function of genetically engineered T cells in the blood of treated melanoma patients.
CARPETS: A Phase I Open Label Study of the Safety and Immune effects of an Escalating Dose of Autologous GD2 Chimeric Antigen Receptor-Expressing Peripheral Blood T Cells in Patients with Metastatic BRAF-Mutant and GD2-Positive Melanoma
Malignant melanoma is increasing in incidence in Australia. Once the disease has reached an advanced stage the prognosis is poor, and the treatment options few. A new drug, called a B-Raf inhibitor, targets a signalling pathway involved in promoting melanoma growth. While this drug has therapeutic effects in a large proportion of patients, disease control is short lived as resistance to the drug inevitably develops. Prof Brown will lead a clinical trial investigating the use of adoptive T cell immunotherapy to target melanoma cells that have become resistant to B-Raf inhibitor treatment. This will involve the genetic modification of the patients own T cells to redirect them against the melanoma; these anti-melanoma T cells will then be reinfused into the patient. The feasibility, safety and immune effects of this therapy will be evaluated in patients who have advanced melanoma that is no longer responsive to B-Raf inhibition.
A combinatorial approach to melanoma therapy: preclinical evaluation of concurrent B-Raf inhibition and adoptive T cell immunotherapy
This preclinical study complements the CARPETS clinical trial and investigates whether concurrent treatment with a B-Raf inhibitor and genetically modified anti-melanoma T cells is feasible. We will evaluate the effect of B-Raf inhibitor on the function of the genetically modified T cells in vitro and the efficacy of combined treatment in vivo in preclinical models of melanoma. It is hoped that this study will provide justification for a future clinical trial combining these therapies.
Novel cancer targeting research projects:
These projects will build on previous published work from our laboratory and extend the application of this unique technology to a broader range of human cancers.
APOMAB® targeting of dead cancer cells for monitoring of cancer therapy
APOMAB® is a monoclonal antibody that binds to a protein that is revealed during cell death. This technology aims to serve an unmet medical need by determining whether a patient’s cancer responds to anti-cancer treatment through the detection of cancer cell death soon after the commencement of treatment. Then, doctors would continue useful treatment and cease useless treatment, thus sparing the patient unnecessary toxicity. We have established that APOMAB® preferentially detects cancers at a late stage of cell death, which is likely to be the stage that is most useful for the clinical application of this technology. Plans are underway to make a clinical-grade APOMAB® product for testing in a first-time-in-human clinical trial.
APOMAB® targeting of dead cancer cells for delivery of cancer therapy
Since APOMAB® can target dead cancer cells, which are created in response to chemotherapy and which lie close to live cancer cells, we reasoned that the APOMAB® antibody could also be used to deliver an anti-cancer treatment such as radioactivity, which can then kill the surrounding live cancer cells. We have proven the case in preclinical cancer models and now wish to show if a more powerful, targeted form of radioactivity in the form of alpha-particles has superior therapeutic effects in the same preclinical cancer models. We believe that this approach may improve anti-cancer treatment without inducing any more damage to normal tissues.
Cancer vaccine research projects:
In these projects, we aim to study fundamental aspects of innate immune function in order to understand how to improve the workings of cancer vaccines.
Using recombinant poxvirus vectors in the development of cancer vaccines
About 20% of human cancers originate after an initial infection such as human papilloma virus (HPV or wart virus) that can cause cancer of the uterine cervix. As the HPV vaccination program has already shown, if these cancer-inducing infections can be eliminated then the subsequent cancers themselves may be prevented. We are developing a platform vaccine vector technology, which could be applied to a number of different types of infections as well to some cases cancer directly and which thus could be used both to treat and prevent these conditions. Although this promising vaccine technology is being tested in current clinical trials for a number of diseases such as HIV, melanoma and prostate cancer, an understanding of how exactly it works is lacking. With an in-depth understanding of the mechanisms underlying the action of this vaccine, we are now in a stronger position to modify these vaccines in order to generate better immune responses, which may translate to improved clinical benefits for patients.
Development of a novel functionalised solid support surface for the detection and analysis of antigen-specific T cells
Any worthwhile vaccine results in the body producing new T cells that are available to fight an ensuing infection or an emerging cancer. The vaccine contains an antigen that is specifically recognised by the new T cells. However, identifying and analysing the properties of these antigen-specific T cells in human blood after vaccination has not been easy task. We are working on methods to improve this task. Consequently, we are developing a device that enables the capture and functional analysis of antigen-specific T cells that can later be applied to the study of blood from vaccinated human subjects. In collaboration with the Ian Wark Research Institute, we are using specialised solid surfaces to investigate the conditions required to capture and stimulate antigen specific T cells. We anticipate that this technology will also be applied to studying the function of genetically engineered T cells given to advanced melanoma patients.
Targeting cancer cells through vaccination
The surface of cancer cells has increased numbers of some signalling molecules when compared to normal surrounding cells. We have decided to see whether we can use this information in the form of two different kinds of vaccine, one virally based, to ‘teach’ the immune system to attack cells based on the expression of these distinct molecules. If successful, the development of such a vaccine would enable us to treat and prevent cancers that express these cancer-specific molecules without harming surrounding, normal tissues.
Cancer-related inflammation research projects:
Inflammation can help to promote cancer or be manipulated to turn the cancer against itself. The overall aim of these studies is to understand the role of an important protein called HMGB1 in sepsis and cancer. A better understanding of its role will enable more precise application of a new kind of antibody that can neutralise activity of HMGB1.
Assessing the neutralising activity of anti-HMGB1 antibodies in serum samples from septic shock patients and in experimental murine models of bacterial sepsis
Sepsis (or overwhelming infection) often causes death in the intensive care unit and may complicate common anti-cancer treatments such as chemotherapy. HMGB1 is secreted during serious infection and can mediate its harmful effects. Blocking HMGB1 activity with antibody can prevent this happening in animal models. We propose to develop neutralising antibodies against HMGB1 that could ameliorate clinical course of sepsis in the hospital.
Assessing the neutralising activity of anti-HMGB1 antibodies in vitro and in preclinical models of cancer
HMGB1 can be secreted by dead and dying cancer cells and push cancer cells toward a type of cell death called autophagy, which can promote resistance to commonly used anti-cancer agents. Blocking HMGB1 activity with antibody may overcome the development of autophagy and help anti-cancer drugs work better to kill cancer cells.
- School of Chemical Engineering, University of Adelaide
- Ian Wark Research Institute, University of South Australia
- Mawson Institute, University of South Australia
- Robinson Institute, University of Adelaide
- Department of Molecular Biosciences, University of Adelaide
- Department of Medical Physics, Royal Adelaide Hospital Cancer Centre
- Cancer Imaging Centre, Peter MacCallum Cancer Centre
- Cell and Gene Therapy Center, Baylor College of Medicine, Houston TX, USA
- Cancer and Vascular Biology Laboratory, John Curtin School of Medicine, ANU
- Medvet Pty Ltd
- ConCA Pty Ltd
- Sementis Pty Ltd
A list of recent publications can be found here.
Fore more information on the Experimental Therapeutics Laboratory, please contact Dr John Hayball on:
Phone: +61 8 8302 1202