Experimental Therapeutics

The Experimental Therapeutics Laboratory is a collaborative venture between scientists from the Sansom Institute for Health Research (University of South Australia), the Hanson Institute, the Cancer Clinical Trials Unit (Royal Adelaide Hospital Cancer Centre).

We perform basic, translational and clinical research that aims to improve chronic and acute health outcomes by exploring novel immunotherapeutic approaches to treat and prevent cancer, allergy and other diseases including chronic and acute infections and uncontrolled inflammation in sepsis and the body’s response to biomaterial implants. Our expertise exploits the specificity and power of the immune system to design, develop, and implement cutting edge approaches to new therapeutic and diagnostic agents.

Industry links, experience and clinical expertise ensure that our research has a strong likelihood of generating applications for potential commercialisation and improved therapeutic outcomes for patients


People

Laboratory head
Associate Professor John Hayball (School of Pharmacy and Medical Sciences, UniSA)

Associate head
Professor Michael Brown (Director Clinical Trials Unit, RAH; Adjunct Professor, UniSA)
(http://centreforcancerbiology.org.au/research/laboratories/translational-oncology-laboratory/)

Collaborative partners
Dr Paul Howley (CEO and CSO, Sementis Pty Ltd; Adjunct Senior Lecturer, UniSA)
Dr Kerrilyn Diener (NHMRC Early Career Research Fellow, UA; Adjunct Senior Lecturer, UniSA)
Associate Professor Krasimir Vasilev ( Mawson Institute, UniSA)
Professor Sarah Robertson (Director, Robinson Research Institute, UA.)
Dr William Smith (Allergy SA and Department of Clinical Immunology and Allergy, RAH; Adjunct Senior Lecturer, UniSA)
Associate Professor Michael Stark and Dr Nicki Hodyl (NICU, Women’s and Children’s Hospital; UA)
Professor Greg Woods and Dr Bruce Lyons (University of Tasmania)
Associate Professor Marianne Chapman (ICU RAH; UA)
Dr Tim Kuchel (Director, Preclinical Imaging Research Laboratory, SAHMRI)

Scientific staff
Dr Tamara Cooper (UniSA)
Dr Liang Liu (UniSA)
Dr Andrew Flies (UniSA)
Dr Erin Lousberg (UA; Adjunct Lecturer, UniSA)
Dr Alex Staudacher (RAH)
Dr Tessa Gargett (RAH)

Research support staff
Mr Christos Mavrangelos (UniSA)
Ms Jamie Zhang (UniSA)
Ms Robyn Kievit (UniSA)
Ms Rosa Katsikeros (RAH)

Research students
Ms Susan Christo (PhD student, UniSA)
Ms Natalie Stevens (PhD student, UniSA)
Ms Melissa Tan (PhD student, UniSA)
Ms Shamika Moore (PhD student, UniSA)
Ms Anita Kral (PhD student, UA)
Ms Nerissa Lakham (PhD student, UA)


Current Competitive Grants and Fellowships

ARC Discovery Grant DP15104212 ‘Surface engineered biomaterials to control inflammation’. K. A. Vasilev and J. D. Hayball. Awarded $330,000 for 2015-17.

Ilhan Food Allergy Foundation ‘Modulating antibody receptor signalling to treat peanut allergy’. J. D. Hayball, A. Flies, W. Smith and B. Tao. Awarded $45,000 for 2015-16.

Channel 7 Children’s Research Foundation Grant ID151079 ‘Modulating Fc receptor signalling to treat and prevent peanut allergy’. J. D. Hayball, A. Flies, W. Smith and B. Tao. Awarded $75,000 for 2015-16.

China-Australia Centre for Health Research Grant. ‘Development of a novel viral-vector based human papilloma virus therapeutic vaccine’. J. D. Hayball, L. Liu and X. Wang. Awarded $20,000 for 2015-16 

Sansom Institute for Health Research Grant .New biomaterials for improved tissue implant performance’. J. D. Hayball and K. Vasilev. Awarded $50,000 for 2014.

Tasmanian Devil Research Advisory Committee Grant ‘Translating successful human cancer immunotherapy techniques to veterinary medicine using naturally transmissible tumours as model systems’ .A. Flies, G. Woods and J. D. Hayball. Awarded $20,000 for 2014-15.

Morris Animal Foundation Fellowship ‘Investigation of cancer immunotherapy for the Tasmanian devil facial tumor disease’. A. Flies, G. Woods and J. D. Hayball. Awarded $200,000 for 2014-16 (MAF, UniSA and UTas).

Sansom Institute for Health Research Grant ‘Translating successful human cancer immunotherapy techniques to veterinary medicine using naturally transmissible tumours as model systems’. A. Flies, G. Woods and J. D. Hayball. Awarded $10,000 for 2014-15.

Robinson Research Institute Innovation Seed Funding Program ‘The development of a new passive immunotherapeutic for the treatment and prevention of sepsis in mouse neonates’. K. R. Diener, J. D. Hayball, M Stark, and N Hodyl. Awarded $25,000 for 2014-15.

AusIndustry Entrepreneur Development “Researchers-in-Business’ Scheme ‘New vaccines for infectious diseases, allergy and cancer’. J. D. Hayball and P. Howley Awarded $150,000 for 2014-15 (Sementis Ltd and UniSA). 

Sementis Ltd. ‘New vaccines for infectious diseases, allergy and cancer’. J. D. Hayball, Awarded $3,000,000 for 2012-15

Sementis Ltd. ‘A new vaccine Chikungunya virus infections’. J. D. Hayball. Awarded $180,000 for 2012-15.

Premiers Science Fund Collaboration Pathways Program ‘Development of diagnostic and prognostic devices and advanced biomaterials for the treatment of kidney disease’. K. Vasilev, J. D. Hayball, J. Gleadle, P.  Majewski, H. Griesser, M. Michael. Awarded $600,000 for 2012-15 (SAGov and UniSA).

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. 


Current research activities

New platform vaccines for immuno-therapeutic or prophylactic applications

The Experimental Therapeutics Laboratory, in collaboration with Dr Paul Howley and Sementis Ltd, is developing a novel vaccine vector platform. This platform is a Vaccinia virus-based live viral vector, and through complicated genetic reformation, the virus has been re-created and aims to be a safer and more efficient vaccine delivery system. By modifying immune-related genes, this live viral vector aims to efficiently express the target antigen, and effectively induce the immune response. More importantly, by controlling virus essential replication-related genes, the vector is designed to have an extremely safe profile. In addition, this vector system can accommodate large sizes of foreign antigen genes and can therefore be used for a range of immunotherapeutic applications, such as allergies, cancer and infectious diseases

Some cancers contains cells that are biochemically distinct from normal cells. We are investigating ways to use this information to develop recombinant viral vaccines that will ‘teach’ the immune system to attack cells based on the presence of these distinct molecules. The development of such a vaccine would enable us to treat and prevent cancers without harming surrounding normal tissues and could be used to improve the outcomes of current therapies. We are currently particularly interested in applying this strategy to prostate cancer and melanoma.

A new vaccine for Chikungunya virus infection

Chikungunya is a mosquito-borne infectious disease causing long term, debilitating, arthritis-like symptoms and even death in severe cases. With severe morbidity, mutations and climate changes that have increased the mosquito host range and distribution, outbreaks are on the increase. In areas where Chikungunya virus has not been endemic, a vaccine is greatly needed. The Experimental Therapeutics Laboratory, in collaboration with Sementis Ltd, is working on a preventative vaccine for Chikungunya, based upon the Sementis proprietary viral vector platform.

The effect of inflammation on reproductive success

The Experimental Therapeutics Laboratory research group and collaborative partner Dr Kerrilyn Diener and Professor Sarah Robertson, have an interest in studying the innate and adaptive immune systems within the female reproductive tract. This is in an attempt to understand their role in dictating the outcome of many conditions including the response to vaccination, infection and pregnancy. The group are currently investigating the role of infection, tolerance and plasmacytoid dendritic cells during different stages of the reproductive cycle and pregnancy to determine whether early infection, or depletion of plasmacytoid dendritic cells throughout pregnancy, can adversely affect the outcomes of implantation and pregnancy and ultimately fetal growth, survival and long term behavioural outcomes.

Immunotherapeutics to treat and prevent Tasmanian devil facial tumour disease

The Experimental Therapeutics Laboratory research group and in collaboration with Professor Greg Woods and Dr Bruce Lyons are currently developing cancer therapeutics to treat the Tasmanian devil facial tumour disease and also to treat cancer in dogs. The immunotherapeutics aim is to block inhibitory checkpoint molecules CTLA4 and PD-1, a strategy which has yielded unprecedented success in treating stage IV human cancers. Additionally, one of the primary means by which the devil facial tumour evades the immune system is via downregulation of MHC class I on tumour cells. We are developing devil facial tumour cell lines that produce IFNγ, which should stimulate expression of MHC class I. These modified tumour cell lines can be used as part of a therapeutic vaccine. These projects have the potential to help save an endangered species, develop new veterinary therapeutics that could become widely used in veterinary medicine, and shed light on how cancer evades the immune system. Students involved in cancer therapeutic design will develop basic molecular biology, immunology, cell culture and genetic engineering skills that will prepare them well for a career in the biomedical sciences.

Immunotherapeutics to treat and prevent peanut allergy and other food allergies

Despite the risk of potentially fatal reactions, there is currently no method available in routine clinical practice for treating peanut allergies. The Experimental Therapeutics Laboratory research group have established a robust murine peanut-induced anaphylaxis model that will be used to test an immunotherapeutic approach which aims to selectively inhibit the production of peanut allergen-specific antibodies and decreases the risk of anaphylaxis during the desensitization process. Together with collaborative partner Dr William Smith we are determining whether this type of immunotherapy could have broad application in treating allergic diseases.

The role of damage associated molecular patterns in sepsis and cancer

The overall aim of these studies is to understand the role of an important protein called HMGB1 in adult and neonatal 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. 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 are developing and testing neutralising antibodies against HMGB1 that could ameliorate clinical course of sepsis in the hospital, both in adults (with collaborative partners Associate Professor Marianne Chapman ) and infants (with Associate Professor Michael Stark and Dr Nicki Hodyl). 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, helping anti-cancer drugs work better to kill cancer cells.

Manipulating the inflammatory response to biomaterial implants

New clinical applications for biomaterial implants are rapidly emerging, and novel approaches to their manufacture and the material from which they will be constructed from are warranted. This is because they need to be able to interact favourably with the body’s defence systems and this project aims to achieve this goal using nanotechnology. With collaborative partner Associate Professor Krasimir Vasilev, we aim to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. We have experimental evidence demonstrating that engineered surface nanotopography in combination with surface chemistry downregulates the expression of proinflammatory cytokines from primary macrophages. These exciting findings are important because they show that it may be possible to engineer the nanotopography of a biomedical device surface in a manner which leads to a desired and predictable level of inflammation and subsequent foreign body reaction (FBR) medical implants and tissue engineering constructs.


Recent publications

A list of recent publications can be found here


Contact

Fore more information on the Experimental Therapeutics Laboratory, please contact Associate Professor John Hayball on:
Phone: +61 8 8302 1202
Email: john.hayball@unisa.edu.au

Areas of study and research

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