Cancer researchers at Peter MacCallum Cancer Centre and Monash University in Melbourne have identified for the first time how a new class of epigenetic drug engages with the immune system to kill off cancer cells.
The research, published in journal Cell Reports, has demonstrated the potential of combining ground-breaking epigenetic and immune-based treatments for improved results.
The experiments showed that immune-competent mice with lymphoma had a far greater response to BET-inhibitors than their immune-deficient counterparts. BET-inhibitors are a relatively new class of cancer treatment, which work to ‘switch off’ important cancer-causing genes expressed within tumour cells.
In addition to the improved response, the research showed that BET inhibitors were able to ‘switch off’ a protein called PD-L1 which is used by tumour cells to hide from the immune system.
Through this mechanism, BET-inhibitors were making tumour cells more sensitive to attack from the immune system.
The power of an activated immune system in eliminating tumour cells has been proven through successful drugs such as Keytruda and Opdivo, which also target the PD-L1 pathway.
Building on this knowledge, Melbourne researchers confirmed that the combinations of BET-inhibitors with other immune therapies work better in lymphoma than either therapy alone.
Based on laboratory research performed at Peter Mac, the Monash team is currently trialling a combination of a different epigenetic drug called Dinaciclib with the anti-PD1 therapy, Keytruda, in relapsed lymphoma, myeloma and chronic lymphocytic leukaemia. Further clinical trials for the combination therapy are likely to emerge as a result of this research.
This research was supported by the National Health and Medical Research Council of Australia; Victorian Cancer Agency; Snowdome Foundation; Cancer Council Victoria; The Kids Cancer Project, and Roche. Core technologies enabling the research are supported by the Australian Cancer Research Foundation (ACRF) and Peter MacCallum Cancer Foundation.
This article was first published on the Peter Mac website, image courtesy of Peter Mac.
To date, ACRF has awarded in total $AUD 8.2 million to support cancer research at Peter MacCallum Cancer Centre and Monash University.