Projects

Stellabody® Technology in Cancer Therapy


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 and Fc receptors on inflammatory cells or by apoptosis through the activation of death receptors.

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. We can modify existing antibody medicines to make them kill more cancers or take antibodies that cannot kill and transform them into potent killers of cancer cells.

Blood cancers include T cell, B cell, myelogenous acute leukaemia, lymphoma and multiple myeloma. We are evaluating the Stellabody® hexamer technology in existing antibody medicines that bind to known targets such as CD20 and CD38 in lymphoma, leukaemia and multiple myeloma. We are also evaluating Stellabody® antibodies to new targets for the treatment of blood cancers. Stellabody® technology not only improves existing medicines by making them more potent killers but also extends the potential use of these existing medicines to cancers that were not previously killed by these medicines. We are evaluating Stellabody® technology and a broad range of antibodies detecting many different targets with a view of progressing to clinical trials.

In solid tumours, such as colon, ovarian and breast cancers, we apply our Stellabody® hexamer technology to induce the death of cancer cells by a process called apoptosis or programmed cell death. Cancer cells display “death receptors”. Use of mAbs that target these “death receptors” do not induce cell death, however, applying the Stellabody® hexamer technology to the mAbs induces extremely potent death signals that kill only the target cells. The on-target hexamerisation by Stellabody® death receptor-specific mAbs increases death receptor clustering on the cell. The clustering amplifies the death receptor signals leading to apoptosis-induced cell death and the elimination of the cancer cells. We are evaluating this against a range of solid tumours with a view to progress into clinical trials.

The complement subcomponent C1q, here resembling a cluster of 6 bent golf clubs, and the proteases C1r2C1s2 twisted amongst the C1q shafts. The Stellabody® modification of the IgG Fc enhances Fc interactions to form an optimal hexameric platform for the binding and activation of the first component (C1) of the classical pathway of complement. The C1 structure is from Mortensen et al., (2017) Proc Natl Acad Sci U S A 114:986-991

Results

We have shown the Stellabody™ modification of anti-cancer mAbs makes them extremely potent killers of cancer cells e.g. CD38 mabs such as Isatuximab and Daratumumab in multiple myeloma, CD20 mAbs in lymphoma, and Death Receptor mAbs in adenocarcinoma.

Collaborators

  • Prof Andrew Wei, WEHI
  • Prof Ross Baker, Perth Blood Institute
  • Prof Joe Trapani, Peter McCallum Cancer Centre
  • Prof Andrew Spencer, Alfred Health
  • Prof John Cambier, University of Colorado
  • Dr Alicia Chenoweth, King’s College London

Funding

  • NHMRC
  • Walkom Bequest
  • Janina and Bill Amiet Foundation
  • Pat & Helen La Manna Cancer/ Stroke Research Legacy
  • Percy Baxter Charitable Trust
  • Harry Secomb Foundation
  • Margaret and John Crutch Bequest

Contact Details

For any general enquiries relating to this project, please contact:

Professor Mark Hogarth

Head, Immune Therapies Group

Telephone

+61392822111

Email

mark.hogarth@burnet.edu.au