A new target in cancer immunotherapy

A new target in cancer immunotherapy

Partnering opportunity in cancer: 

A new target in cancer immunotherapy

 

Team

Dr Nick Huntington, Dr Sandra Nicholson, Dr Jeff Babon

Background

Immunotherapies harness a patient’s adaptive immune system to fight tumour cells that were previously evading T cell response. As a reflection of their impact, first generation immunotherapies are expected to become the highest selling drugs of all time, with sales forecast to exceed $80 billion per annum by 2020.

However while they have been transformative, many patients fail to respond. As a consequence, research has focused on exploiting the innate immune system, particularly natural killer (NK) cells.

These cells have the ability to detect aberrant expression of proteins on the surface of cancer cells and kill them directly. This activity is governed by the integration of signals from activating and inhibitory ligands, and from cytokines such as IL-12, IL-18 and IL-15. The pleiotropic cytokine IL-15 is an important regulator of NK cell development, homeostasis and activation. Systemic delivery of IL-15 has been trialed as a cancer therapy, however enthusiasm for its use has been tempered by toxicity. Thus novel approaches to enhance IL-15 activity that render NK cells more responsive to IL-15 are appealing avenues for investigation.

The technology

Our researchers have identified CIS (cytokine-inducible SH2-containing protein) as a key suppressor of IL-15 signaling in NK cells. CIS-deficient (Cish-/-) NK cells are hypersensitive to IL-15 and as a result, CIS-deficient models are resistant to experimental melanoma metastasis, more so than the combination of anti-PD-1 and anti-CTLA-4 antibody treatment - currently the gold standard immunotherapy treatment against advanced melanoma. Loss of CIS results in heightened and prolonged IL-15-driven JAK-STAT signaling in NK cells. We believe CIS interacts with JAK1 to switch off IL-15 signalling, thus preventing metastasis formation. We therefore propose the CIS-JAK1 interaction may form the basis of new cancer immunotherapies.

Applications

The inhibition of CIS may be effective in any disease amenable to NK cell activation including solid tumours, blood cancers and viral infections such as herpes simplex virus and influenza.

Intellectual property

A provisional patent application has been filed.

Opportunity for partnership

We are seeking a partner to invest in the development of novel small molecule compounds with activity against CIS via high throughput screening, fragment screening and medicinal chemistry, as well as in the pre-clinical development of these molecules.

Key publication

  • Delconte RB. et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nature Immunology. 2016 Jul;17(7) 816-824 PMID: 27213690

Contact

Dr Lauren Giorgio, Business Development Associate

Phone: +61 3 9345 2779 Email: giorgio.l@wehi.edu.au

 

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