Medical School

Postgraduate research profiles

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Wayne Aston

Phone: (+61 8) 6151 1081


Supervisors

Start date

Feb 2015

Submission date

Feb 2018

Wayne Aston

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Thesis

Cancer Chemo Immunotherapy - Exploiting the Immunogenic Momentum of Cytotoxic Chemotherapy

Summary

Cytotoxic chemotherapy is current the gold standard of treatment for many cancers but unfortunately is often not curative. Many cancers such as malignant mesothelioma are resistant to this and other treatment regimes and so new approaches need to be developed.

Recently, much research has focused on understanding the immune-suppressive environment of cancers and how this can be exploited to develop new, better therapies. These treatments include drugs that target ‘immune checkpoint molecules’. These are negative receptors found on immune cells that shut down immune responses. By blocking these receptors with targeted antibodies, we can remove the ‘brakes’ on an immune response that can now last longer and be more effective at eradicating tumour cells. Although these therapies have recently shown great promise in the treatment of several cancers resulting in long-term regression of the disease, most patients unfortunately do not respond to them.

For a long time it was thought that cancer chemotherapy was immune-suppressive and could not be combined with these antibodies. However, recent findings have shown that chemotherapeutic agents can have immune-stimulating properties. For example, tumour cells can release immune activating signals when they are killed by chemotherapy, suppressive cell types can be deleted and checkpoint molecules can be inhibited (Figure 1). These findings strongly argue for the combination of chemotherapy and checkpoint blockade which would exploit the cancer-killing capacity of chemotherapy and the immune-activating potential of checkpoint blockade.

Why my research is important

There are 2 primary questions that my research focuses on: What are the immunological effects of the different chemotherapeutics and how can we combine them with immune checkpoint blockade in the most optimal manner? By determining which chemotherapeutics are immune-stimulating and if or how they synergize with checkpoint blockade therapy, we can potentially discover a combination that significantly improves patient outcome. As these therapies are already developed and approved for clinical use, translation to the clinic can be done effectively and relatively quickly.

Funding

  • This project is funded by NHMRC project grant # 1067113 ‘Cancer Chemo Immunotherapy - Exploiting the Immunogenic Momentum of Cytotoxic Chemotherapy’, and supervised by Dr. Willem Joost Lesterhuis, Prof. Richard Lake, Prof. Anna Nowak and Dr Scott Fisher.

Figure 1: The immunogenic effects of chemotherapeutics (Aston et al, 2014).