Improving the efficacy of cancer, inflammation and infectious disease treatments.
Therapeutic antibody technologies have revolutionised treatments across a spectrum of diseases including cancer, infectious diseases and autoimmunity. However, these treatments have hit a natural potency ceiling as unmodified antibodies, as they occur in nature, do not aggressively engage the immune system. This means unmodified ‘natural’ mAbs are limited in their effectiveness as treatments for eliminating disease cells or for communicating with cells.
Stellabody® hexamer technology breaks through these limitations. It’s a transformative discovery that makes use of the multifunctional application of antibodies to disease but dramatically improves the potency of these antibodies and antibody-like biologics. This leads to the creation of function-enhanced therapeutics for the treatment of cancer, inflammation and infection.
The technology is a change to the Fc tail of antibodies which exploits their natural behaviour, resulting in the formation of hexameric clusters of the antibodies after they bind to their target.
These Stellabody® hexamers are the ideal launching pad for potently firing immune effector systems or to amplify communication signals to cells. Stellabody® enables antibodies to kill disease targets by the complement system and can communicate cancer cells to initiate a cell death process called apoptosis.
The development of antibody and biological therapies has two key challenges:
Molecular engineering is needed to:
This is where Stellabody® technology comes in.
Stellabody® hexamer technology was discovered in the Immune Therapies group at Burnet Institute, a globally recognised laboratory in this field.
Professor Hogarth has researched antibodies, their effector functions and roles in immunity and inflammation for over 30 years.
The graph shows Stellabody® modification's powerful immune killing of a cancer, far surpassing the antibody used in standard-of-care treatment which is ineffective. It highlights the potential effectiveness of Stellabody® in treating patients with cancer.
Stellabody® hexamer technology works by exploiting the normal biology of antibodies and drives them into formation clusters of six antibodies (hexameric clusters) once they have bound to their target e.g. cancer cell.
Just as flags help in co-ordinated attacks on battlefields, Stellabody® 'on-target' hexamers communicate a powerful danger pattern to the immune system to initiate effector responses to kill targets.
Molecular patterns are important beyond the function of the immune system. Communication by patterns is a fundamental property of cells and this often occurs through cell surface receptors. In an alternative application, the Stellabody® hexamer pattern can communicate the amplification of the signals of mAbs binding cell surface receptors.
Either way, by communicating with immune effector functions or through cell surface receptors, Stellabody® hexamers confer potent actions on antibody or antibody-like biologicals.
Human serum contains a collection of proteins called the complement system which is one of the most powerful destructive systems used by antibodies.
The Stellabody® antibody hexamers create the optimal platform for the landing and activation of the first components that trigger this complement 'cascade' system to kill disease causing cell targets.
Cell surface receptors normally deliver signals between cells. Antibodies or antibody-like molecules can poorly cluster these receptors and deliver weak signals.
Stellabody® technology clusters these receptors into hexamers which in turn initiates more powerful signals. This amplification of signals can be applied to ‘death receptors’ on cancer cell so that the Stellabody® hexamer patterning of these receptors strongly initiates a ‘self-destruct’ program that results in the death of the targeted cancer or immune cell.
The Stellabody® hexamer pattern may be used to communicate, particularly through TNFSF receptors, to a variety of immune cells to expand their number or activity. The applications are many, as are the opportunities for partnerships in varied biological systems.
Stellabody® is a powerful and versatile technology adaptable to multiple antibody formats against a broad range of targets, with applications in a wide range of disease settings across cancer, inflammation and infectious disease.
In blood cancers, we are evaluating the Stellabody® hexamer technology in existing antibody medicines that bind to known targets in lymphoma, leukaemia and multiple myeloma. We have shown the Stellabody™ modification of anti-cancer monoclonal antibodies (mAbs) – such as isatuximab and daratumumab (CD38 mAbs) in multiple myeloma and CD20 mAbs in lymphoma makes them potent killers of cancer cells. We are also evaluating Stellabody® antibodies to new targets for treatment.
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. Applying the Stellabody® technology to mAbs that target ‘death receptors’ on cancer cells 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. This clustering amplifies the death receptor signals leading to apoptosis-induced cell death and the elimination of the cancer cells.
Potent biologicals for the prevention and treatment of COVID-19, with extensions to other infectious diseases such as malaria and those caused by viral (e.g. HIV) or bacterial pathogens.
By combining an engineered form of the human receptor for SARS-CoV-2 and the Fc portion of an antibody into one biological drug, and applying Stellabody® technology, we have developed therapeutics to prevent and treat COVID-19 and other coronavirus diseases.
We are also seeking novel targets and new antibodies for a broader range of infections including key hospital acquired infections by antibiotic resistant microbes and emerging viruses to which we can apply the Stellabody® technology.
Burnet Institute has entered into a Research Licence and Option Agreement with biopharma company argenx for a ground-breaking technology able to transform the way we approach cancer, inflammation and infectious disease treatment.
Immunological Reviews
Clarissa A. Whitehead, Bruce D. Wines, Halina M. Trist, Sandra Esparon, P. Mark Hogarth
Frontiers in Immunology
Bruce D. Wines, Liriye Kurtovic, Halina M. Trist, Sandra Esparon, Klasina Chappin, James G. Beeson, P. Mark Hogarth
This slide deck contains more information about the Stellabody® technology and our associated patents.
Stellabody® information deck [PDF 2.5 MB]