The University of Queensland
Tackling the root cause of cancer immunotherapy resistance

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SUMMARY

Many cancer patients are resistant to current immunotherapy and have few further options. Current immunotherapies target specialised immune cells, which can kill cancer cells.  If these immune cells are initially absent in the tumour, patients will likely not respond to immunotherapy. 

We previously thought that immune suppression installed by the tumour is detrimental to outcome. I discovered that patients with high immune activity inside the tumour typically also have high levels of immune suppression, and paradoxically both are associated with good prognosis. Patients without immune activity within the tumour are often those who don’t respond to immunotherapy, and represent a group of high unmet need for new approaches.

My research discovered key components that drive or hinder an initial tumour immune response. This work led to identification of potential drug targets. I now develop a new generation of therapies targeted to patients without tumour immune activity to overcome therapy resistance.

BENEFIT – A description of the benefit of your work to Queensland (max 500 words)

More than 27.000 people, on average one every 20 minutes, are diagnosed with cancer every year in Queensland. More than 8700 people per year will succumb to the disease. 

Traditional cancer therapies comprise surgical removal, radiotherapy and chemotherapy. The advent of new cancer immunotherapies has revolutionised the medical cancer field, and have greatly benefitted those who respond. Unfortunately, the past years have revealed that these new therapies benefit, depending on cancer type, on average only 20% of patients, at a cost of approximately AU$180.000 per patient per year, excluding costs of associated medical care. The 80% of non-responding patients are left with few treatment options, and hence represent a cohort of cancer patients with great need for alternative therapies. 

The big hurdle to overcome therapy resistance lies in the identification of new biomarkers that will predict therapy response, and the development of new therapies suitable for this patient cohort. These new therapies require development of new drugs that work by different mechanisms than those currently available. 

My research aims to develop these new drugs, which will be targeted at a specific immune cell that acts as synthesizer and is positioned at the root of tumour immunity. These so-called antigen-presenting cells play a key role in activating and licencing tumour-specific killer cells. As double-edge sword, antigen-presenting cells can facilitate this action, or can hinder it, the latter being detrimental for disease outcome. Antigen-presenting cells often are dysfunctional within the tumour, and no therapy currently exists to restore this dysfunction. My vision is to restore antigen-presenting cells within the tumour through drug-specific targeting, which will kickstart an event cascade that initiates tumour immunity and increase patient outcomes. 

Similar to the success of Queensland’s own Prof. Ian Frazer’s cervical cancer vaccine, the successful development of such new cancer therapies will once again revolutionise the way we treat cancer, save lives, and will bring Queensland to the global forefront of discovery and innovation. This will come with economic growth in the biotech space, global recognition for excellence in knowledge and innovation and importantly, new clinical trial options for Queensland cancer sufferers.  I have been mentored as an early career researcher in Prof. Ian Frazer’s laboratory and have completed a four-year position as a Senior Scientist in a biomedical company developing immune therapeutics. This experience and my current location at the Translational Research Institute, co-located with the Princess Alexandra Hospital and Pharmaceuticals Australia Centre of Excellence (PACE), means my ability to translate my research to clinic is supported within an excellent translational environment. My global recognition as antigen-presenting cell expert is evidenced by acquisition of international collaborations and funding, and invitations to present at relevant international conferences, where I represent Queensland’s capacity to carry out cutting-edge research.

ROLE MODEL – Why do you think you are a good role model for women and girls aspiring to work in STEM? (max 500 words)

Through my various roles in academia and industry and through my engagement and STEM promotion activities I have found a maturation from seeking role models to becoming a role model. Through my roles in engagement with schools and the public I have learned that I am viewed not only as a woman in science, but as a smart, determined scientist and mother. 

Within the UQDI Lean-In circles I am able to share my experience with other women in STEM. Mentoring can take many forms, from aiding in grant preparation and advising on career progression to informal discussions on balancing work and family commitments. My experience as a Senior Scientist in Industry is welcomed by my peers and aspiring young women in science. 

As women in science we often suffer “imposter syndrome” and our learned modesty through our environmental conditioning from a young age often prevents us from reorganising our potential as role models. I have learned that I am viewed as strong, determined, successful and an excellent researcher. I am a committed parent and have juggled all my commitments to work and family successfully. I am now empowered to encourage other women and girls in STEM careers. The joy I find in science and work while at the same time enjoying motherhood is viewed as a positive example. Importantly, I am keen to devote time to mentoring young women in science and engaging in community events, particularly school events, to serve as an example of how much life and work satisfaction can be derived by being a woman in STEM. 

This role I think becomes particularly important in engagement with cancer patients. People traversing their cancer journey face many trials and fears. Science and medicine are sometimes viewed with suspicion. An important part of being a woman in STEM and cancer science as well as a mother is my ability to both empathise and connect with patients and reassure them, as a role model of humanity and normality, that researchers in science and medicine have only care and best intents for patients. This public role has assumed more significance through the Covid-19 pandemic. An important role for all researchers now, men and women, is to connect with the public and strengthen fact-based research and education. 

ENGAGEMENT – Describe any STEM promotion or engagement activities that you have undertaken, including both scientific and non-scientific audiences, particularly with women and girls (maximum 500 words)

While our recent external engagement activities have been curtailed by the Covid-19 pandemic, my passion for STEM engagement has been continued in various forms:

In 2019 I published a science article in a journal for children, and peer-reviewed by children (Frontiers for Young Minds). This article is aimed for a primary school audience, describing the biology of HPV and warts. 

At my institute and as member of the UQDI Equity, Diversity & Inclusion committee, I spearheaded a ‘Lean In’ circle in 2019. This circle is a group of female researchers that meet monthly with the aim to develop leadership skills, overcoming hurdles of inequality, provide peer-mentoring and a supportive network. One of the recurring themes in this circle is confidence, and together, we assess our competencies, hone our visions, and create action plans to meet our goals.  Within this circle, we achieved and celebrated successes in promotions, grants and awards. 

Since 2022, I have volunteer for the Australian Cervical Cancer Foundation (ACCF). I trust this will develop into a standing engagement opportunity. I am currently revising teaching materials, where ACCF engages with high school students to educate about cervical cancer prevention. My revisions focus specifically on using inclusive language that engages all identities. While cervical cancer is the dominant cancer induced by HPV, it is not the only one, and HPV is also responsible for cancers in other anogenital areas and within the throat. While in the past HPV education was primarily directed to women due to its high prevalence of cervical cancer, it is now important that we reach all young people, irrespective of gender identity, and I am hoping to make a meaningful contribution in this area. With Covid-19 restrictions permitting, I am working with ACCF towards visiting high schools and delivering these educational presentations, where I can contribute my experience as a woman in STEM scientist working in the field of cervical cancer. 

As mother, I engage regularly with my children’s schools to promote STEM. I delivered a science presentation at my son’s kindergarten program, where I performed experiments with the children on the topic of states of matter. For this, I dressed up in appropriate lab wear, I introduced the children to the three states of matter and its conversion reactions using interactive games, and I performed a Smoking Bubbles Dry Ice Experiment. I later received feedback from mothers of girls that told me how intrigued the girls were to meet a real scientist that is a mother! During my son’s year 2 at primary school, I went to the classroom for a science presentation on the topic of HPV and warts. I explained to the children basic concepts of translational research, viruses, and how warts are formed. The children asked many enthusiastic questions and later called me out in the playground as “the real scientist woman!”. My son later told me that many of his female school friends were excited that his mum was a scientist. 

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