Grant Stories
Ironing out IBD: a new grant in the crusade against anaemia of inflammation
In Australia, IBD is a significant health concern affecting an estimated 100,000 people, and cases are on the rise. It encompasses two main conditions: Crohn’s disease and ulcerative colitis, both of which involve chronic inflammation of the gastrointestinal tract. Known as anaemia of inflammation, an estimated 30% of IBD sufferers will experience anaemia from their disease. It is also seen in patients who suffer other inflammatory and autoimmune diseases.
Patients with anaemia of inflammation often have low levels of iron in their blood because the inflammation impacts the body’s ability to utilise stored iron, which is needed to make healthy red blood cells, thereby leading to anaemia and potentially resulting in insufficient oxygen supply to the body’s tissues.
The LINC (Leading Innovations through New Collaborations) program was co-developed by TRI, Metro South Health and Mater Research in 2021 and provides up to $50,000 in seed funding for new research projects with clinical applications. The program provides dedicated seed funding for new research collaborations between early to mid-career researchers based at TRI and early to mid-career clinicians based at Metro South, Mater or the Queensland Children’s Hospital.
Key points
- Research: To better understand the mechanisms of anaemia in Inflammatory Bowel Disease (IBD) patients, with the goal of finding new therapies to treat this common IBD symptom.
- Amount awarded: $49,947.
- Awarded to: Mater Hospital Head of Inflammatory Bowel Disease Dr Yoon-Kyo An and Mater Research Senior Research Officer Dr Kavita Bisht.
- Grant scheme: Leading Innovations through New Collaborations (LINC).
- Funded by: TRI and Mater Research.
- Year granted: 2021.
Dendritic cell involvement in fighting cancer
Dendritic cells are part of the immune system and are found in the skin, blood and the inner lining of the nose, lungs, stomach and intestines. They are not usually abundant at tumour sites, but an increased density of dendritic cells at the sites has been linked to better treatment outcomes for patients.
There is evidence that some dendritic cells can trigger T-cell activity to suppress tumour growth and aid in controlling cancer progression. In research models, dendritic cells have also been shown to contribute to the success of cancer immunotherapies.
Improving treatment and survival rates
Professor Radford joined Mater Research to develop a dendritic cell vaccine that was translated into a first-in-man clinical trial for metastatic prostate cancer. The trial demonstrated the efficacy of a dendritic cell-based vaccine for treating prostate cancer.
Her research group also first characterised the rare human cDC1 dendritic cell subtype and identified its importance for triggering anti-tumour and anti-viral immune responses. She has been pursuing the therapeutic potential to develop vaccines that will ultimately harness human cDC1 dendritic cells in clinical trials.
A $670,000 grant from the Ovarian Cancer Research Foundation announced in March 2024 will support Professor Radford in developing a vaccine targeting dendritic cells to treat ovarian cancer.
“Research models will aid in better understanding of human cell biology and evaluating immunotherapies”
The future of cancer treatment
Professor Radford says ovarian cancer is challenging to treat because it comprises more than 30 distinct disease types, many of which don’t respond to conventional chemotherapy and standard care protocols.
“Some of the current treatments that are available for women with ovarian cancer have not fundamentally changed in decades,” she says.
“In ovarian cancer patients the dendritic cells are somewhat dysfunctional, which might help explain why, to date, ovarian cancer hasn’t responded to immunotherapy as well as other cancers.”
The Ovarian Cancer Research Foundation grant will enable Professor Radford’s team to investigate which molecules on dendritic cells can be targeted to train the immune system to more effectively fight ovarian cancer.
“We are working on next-generation models for human immuno-oncology,” she says. “They are valuable models for understanding human dendritic cell biology and evaluating new human cancer immunotherapies.
“Immunotherapies are already game changers in the clinic for some types of cancer, but they don’t work for everyone and are often fraught with side effects. The models we are developing represent a new frontier that will facilitate the development of the next generation of more effective immunotherapies.”
Human Immune Model Facility
Professor Radford’s expertise in the field has led to the development of a preclinical research model using human stem cells, capable of generating functioning human immune cells, including dendritic cells.
The research model is core to the establishment of TRI’s new core Human Immune Model Facility, which aims to bridge a critical gap in biomedical research for Australian researchers and industry.
The facility will offer researchers and industry the most advanced, gold standard models for faithful replication of a human immune system for studying disease biology and progression, drug screening and accelerating research translation.
HIMF will benefit from TRI’s Gnotobiotic Facility, located within the TRI Biological Research Facility and capable of supporting germ-free and gnotobiotic experiments – ensuring the elimination or control of microbiota in preclinical models, which is a growing area of focus for research into numerous diseases.
The facility will contribute to significant advancements in medical research in fields such as oncology, hematology, immunology, autoimmunity, infectious diseases, and inflammation; and developing therapeutics for diseases including cancer, type 1 diabetes and Alzheimer’s disease.
Publications
Phillip Johnson, Nikita Rosendahl, Kristen J Radford. Conventional type 1 dendritic cells (cDC1) as cancer therapeutics: challenges and opportunities (2021). DOI: 10.1080/14712598.2022.1994943
Yoke Seng Lee, Liam J O’Brien, Carina M Walpole, Frances E Pearson, Ingrid M Leal-Rojas, Kelly-Anne Masterman, Victoria Atkinson, Andrew Barbour, Kristen J Radford. Human CD141+ dendritic cells (cDC1) are impaired in patients with advanced melanoma but can be targeted to enhance anti-PD-1 in a humanized mouse model (2021). DOI: 10.1136/jitc-2020-001963
M H Lahoud, K J Radford. Enhancing the immunogenicity of cancer vaccines by harnessing CLEC9A (2021). DOI: 10.1080/21645515.2021.1873056
Sreekumar Balan, Kristen J Radford, Nina Bhardwaj. Unexplored horizons of cDC1 in immunity and tolerance. DOI: 10.1016/bs.ai.2020.10.002
Kelly-Anne Masterman, Oscar L Haigh, Kirsteen M Tullett, Ingrid M Leal-Rojas, Carina Walpole, Frances E Pearson, Jonathon Cebon, Christopher Schmidt, Liam O’Brien, Nikita Rosendahl, Ghazal Daraj, Irina Caminschi, Eric H Gschweng, Roger P Hollis, Donald B Kohn, Mireille H Lahoud, Kristen J Radford. Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells. DOI: 10.1136/jitc-2020-000691
Frances E Pearson, Kirsteen M Tullett, Ingrid M Leal-Rojas, Oscar L Haigh, Kelly-Anne Masterman, Carina Walpole, John S Bridgeman, James E McLaren, Kristin Ladell, Kelly Miners, Sian Llewellyn-Lacey, David A Price, Antje Tunger, Marc Schmitz, John J Miles, Mireille H Lahoud, Kristen J Radford (2020). Human CLEC9A antibodies deliver Wilms’ tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1-specific CD8+ T cells. DOI: 10.1002/cti2.1141
Yoke Seng Lee, Kristen J Radford. The role of dendritic cells in cancer (2019). DOI: 10.1016/bs.ircmb.2019.07.006
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford. Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3 and TLR7/8 ligation (2018). DOI: 10.1111/imcb.12009
Yoshihito Minoda, Isaac Virshup, Ingrid Leal Rojas, Oscar Haigh, Yide Wong, John J Miles, Christine A Wells, Kristen J Radford. Human CD141+ Dendritic Cell and CD1c+ Dendritic Cell Undergo Concordant Early Genetic Programming after Activation in Humanized Mice In Vivo (2017). DOI: 10.3389/fimmu.2017.01419
