IGFBP-2 mutant potently inhibits proliferation of neuroblastoma cells

Key Inventor

Professor George Werther
Dr Vince Russo

Summary of the opportunity

An important step in the progression of a large number of cancers is the binding of a prominent growth factor (insulin-like growth factor binding protein-2 (IGFBP-2)) to the cells periphery. Researchers at Murdoch Childrens have demonstrated that a mutant form of IGFBP-2 dramatically reduces proliferation, migration and invasion of cancer cells. This discovery forms the basis of a staged, pre-clinical, cancer drug discovery program.

The Problem / Target Market

IGFBP2 is highly expressed in numerous cancer cells (prostate, ovarian, breast and gastric cancer, acute myeloid leukemia, melanocytic lesions, meningiomas and gliomas).  IGFBP-2 enhances metastatic activity in vitro and in vivo. Approximately 15,000 people die per annum in the US from glioma's alone, with at present very few treatment options other than surgery. IGFBP-2 offers a novel target in an area where current treatments are unsuccessful.
10.9 million people worldwide are diagnosed with cancer annually and there are 6.7 million deaths from the disease. It is estimated that there are 24.6 million people alive who have received a diagnosis of cancer in the last five years. The large patient populations reflect both the potential commercial market and the competitiveness in this area. Although the sales of the top 20 cancer drugs in the seven major markets are expected to be $24.5 billion in 2006 (Datamonitor July 2007), there is the issue of patent expiration with the current therapies and there is a large potential for investment into new therapies and novel targets

Technology, State of Development and Competitive Edge

Our studies demonstrate that IGFBP-2 is a target for cancer therapeutics.  IGFBPs act as carriers or transporters of Insulin-like Growth Factors (IGFs) and may enhance or inhibit IGF activities. Murdoch Childrens researchers have demonstrated that IGFBP-2 can bind to specific integrins on the cell membrane and in the absence of IGF-1 to facilitate IGF independent tumour cell growth. Moreover, in vitro, over-expression of wild type (WT) IGFBP-2 results in dramatically enhanced cell proliferation and invasion of slow growing, non-tumorigenic neuroblastoma (NB) cells. Importantly, when mutant IGFBP-2 is added to these same NB cells, WT- IGFBP-2, cell proliferation and invasion was inhibited. Together these results indicate that mutant IGFBP-2 based drugs can become anti-proliferative agents, even in the presence of endogenous WT- IGFBP-2.
Preliminary in vivo studies, utilising the chick embryo chorio-allantoic membrane (CAM assay) showed that over-expression of WT- IGFBP-2 promoted local angiogenesis and invasion of NB cells within the CAM. In contrast, NB cells over-expressing the mutant IGFBP-2 did not result in local angiogenesis or invasion of NB cells within the CAM. Thus we have identified a novel cancer target and have initial in vivo proof of concept data which confirms that a mutant peptide to this target can suppress tumourogenesis.
New Cancer Therapeutics based on novel target (IGFBP-2)

Nature of the Deal

The Murdoch Childrens Research Institute has patented the technology and is looking to identify and secure a licensing partner in the pharmaceutical or biotechnology industry to contribute to the development of the technology. Murdoch Childrens is seeking an up-front license fee and an annual royalty for the use and application of the technology by the licensee. Royalties would also be payable in the event the licensee wishes to sub-licence the use of the technology for an agreed purpose.