Therapeutics Opportunity

QIMR BERGHOFER IS DEVELOPING THERAPEUTIC INTERVENTIONS FOR A NUMBER OF DISEASE AREAS

 

G9a

Breast cancer is the leading cause of female cancer deaths worldwide and with an estimated 1.7 million new cases every year. The histone methyltransferase enzyme G9a is over expressed in many malignancies, including breast cancer, and effects regulation of genes involved in tumour progression. G9a is also an epigenetic regulator of the known oncogene MYC; long viewed as a potential target for novel therapeutics. QIMR Berghofer researchers, in partnership with drug discovery CRO Domainex, have developed a small molecule inhibitor of G9a which shows promising in vitro and in vivo efficacy against breast cancer. We have demonstrated that tumours derived from tamoxifen resistant cell lines are re-sensitised to tamoxifen when combined with a G9a inhibitor, with the combination inducing tumour regression.

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PDL2

Immunotherapies work by stimulating the immune system to kill only cancer cells. When PD1 on T cells binds PDL1 on DCs or tumour cells, T cells stop functioning. Antibodies directed against PD1 “take the brakes off” the immune system, allowing T cells to mount an effective attack against cancer. However many patients do not respond to anti-PD1 therapy. Recent studies have shown that PDL2, unlike PD-L1, is not a brake on the immune system. A novel multimeric form of soluble PDL2 protein (sPDL2) has been developed at the QIMR Berghofer. Our novel sPDL2 protein is an innovative therapy which both effectively blocks the PD1/PDL1 pathway due to the multimeric nature of PDL2 and directly activates T cells. Our companion diagnostic would significantly improve the accuracy of selecting patients who would respond.

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