Immune Therapies Group

Head: Professor Mark Hogarth

Overview

We are focused on manipulating the immune system to treat human diseases by applying our research discoveries, made over three decades, to the development of potent new biological drugs. We study how antibodies - a natural product of the immune system - switch the immune system on and off and how we can use this to kill unwanted cancers and infections or prevent destructive inflammation and allergies.

Every antibody is composed of two functional parts that provide two distinct roles – the Fab and Fc. The Fab is unique in each antibody and specifically detects a target. Importantly, the Fc portion is common to all antibodies. Our focus is on the activation of immune resistance performed by the antibody’s Fc portion - the critical part that initiates or controls the effector responses. Since the Fc portion is constant in every antibody, our discoveries of how to transform the immune activation responses in one antibody can transform the action of all.

Our primary goal is to discover new ways to treat disease by manipulating antibodies and the immune system. Our discoveries have broad implications for new treatments and wide application of our technology is possible. Our discoveries have led us to create powerful antibody-based biological drugs which will form the basis of next generation, “next-gen“, therapeutics.

Stellabody® hexamer technology is one of our key discoveries. It is a simple but revolutionary and multifaceted technology that is broadly applicable in the development of new biological medicines. The Stellabody® technology was made by a simple modification in the Fc-portion of the antibody. Since the Fc portion is constant in all antibodies, this change can be applied to all antibodies.

The Stellabody® modification drives antibodies to form hexamers which critically form only after the antibody detects its target. This on-target hexamerisation, for example on a cancer cell, virus or parasite, has multiple consequences. The Stellabody® hexamers form the ideal structure to activate the complement cascade – an amplifiable system of blood proteins that delivers powerful killing responses. For example, by converting monoclonal antibodies (mAbs) that target blood cancers into Stellabody® mAbs, they become powerful killers of myeloma and lymphoma cells. Separately, the on-target hexamerisation also clusters the target molecules on the cell which can enhance any signalling capacity by the target to generate more potent responses by the cell. For example, Stellabody® mAbs force death receptors on cancer cells to initiate death of the cell in a process called apoptosis.

Using this technology we can transform the actions of antibodies into potent killers of cancer, potentiating them to be as much as 100 times more effective at killing. A special type of antibody, monoclonal antibodies (mAbs), are being used as biological medicines in cancer infection and inflammation. We can modify existing mAb medicines to make them kill more cancers or even more importantly, modify mAbs that cannot kill and transform them into potent killers of cancer cells.

We have applied the same technology in novel COVID-19 biological drugs called fusion proteins. These drugs can neutralise all SARS-CoV-2 variants and by using Stellabody® technology, they are also potent activators of the immune system which then eliminates the neutralised virus. These drugs will protect us against future pandemics of this type.

There is a serious unmet need in treatment of inflammatory diseases where the immune system is hyper-activated and lacks control. We have engineered the next generation of monoclonal antibody therapies which target inflammatory cells to switch off life-threatening, destructive inflammation.

We modified the Fc portion of the antibody by simple mutation that is distinct from our Stellabody® technology. These mutations allow us to generate antibodies that selectively engage immune cells (white blood cells).

Our research programs on the modifications of antibodies are now being applied in cancer, infectious disease, autoimmune inflammation, and allergy.

Pictured above: Molecular structure of an IgG antibody

Cancer: We are applying our multifaceted Stellabody® hexamer technology to direct the human immune system to destroy cancer cells either by activation of the complement system, Fc receptor binding on inflammatory cells or activation of apoptosis through death receptors. Because of the broad utility of the Stellabody® technology we are working closely with our clinical collaborators to develop and apply Stellabody® mAbs across a range of cancers including rare cancers. These are major projects. We are focused on using our Stellabody® mAbs on blood cancers particularly leukaemia, multiple myeloma and lymphoma. Our work on solid cancers includes colon, prostate, ovarian and we are seeking further partnerships in skin cancers, brain and kidney.

Infectious disease: We have two streams of translational research in this program. First is our unique approach to COVID-19 treatment. We have generated novel biological drugs that are potent activators of the immune system which then eliminate the neutralised virus. The second translational research stream applies the Stellabody® technology and mAbs directed against different pathogens, particularly malaria and HIV.

Inflammation and Allergy: We have discovered how to engineer antibodies to selectively engage inflammatory cells to switch off inflammation that occurs in autoimmune diseases or allergic diseases. Our first project is applying the technology to the targeting of B cells and inflammatory cells that initiate the inflammation and tissue destruction in lupus. The second project studies the application of the technology in allergic disease by targeting allergenic cells. In both projects, our aim is to switch off these cells early and thereby prevent the inflammatory disease.

PARTNERSHIPS: Our remarkable technology is broad-based and is applicable to new treatments for many diseases. The universal nature of our Fc discoveries has wide-ranging implications for the generation of new biological drugs. We are seeking collaborative research partnerships and commercial partnerships to take this technology into clinical testing to develop the next generation of targeted, efficacious treatments for human disease.

SUPPORT: We especially appreciate the unwavering support of our donors over many years who have supported our vision of harnessing the immune system to treat major human disease. We acknowledge Margaret Walkom Bequest; Janina and Bill Amiet Foundation; Pat (OAM) & Helen La Manna Cancer/ Stroke Research Legacy; Percy Baxter Charitable Trust; Harry Secomb Foundation; Margaret and John Crutch Bequest; Nancy E. Prendergast Charitable Trust; Peter Leith Riddell Memorial Fund.

Highlights

Development of Stellabody® technology and its application to create new and powerful therapeutic biological drugs which transform the killing potency of monoclonal antibodies enabling our development of new treatments for cancer and infection.

Contact Details

Professor Mark Hogarth

Head, Immune Therapies Group

Telephone

+61392822111

Email

mark.hogarth@burnet.edu.au

Projects

  • Fc Receptor Targeted Treatments in Inflammation and Allergy

  • Stellabody®

  • Stellabody® Technology in Infectious Disease – COVID-19 and beyond

  • Stellabody® Technology in Cancer Therapy

Staff Members

  • Doctor Bruce Wines

    Doctor Bruce Wines
    Senior Research Officer, Immune Therapies Group

  • Professor Mark Hogarth

    Professor Mark Hogarth
    Head, Immune Therapies Group

  • Neeru  Varese

    Neeru Varese
    Program Manager

  • Reema Bajaj

    Reema Bajaj
    Protein Chemist

  • Sandra Esparon

    Sandra Esparon
    Senior Research Assistant