Our research
The Translational Cancer Immunotherapy Laboratory investigates the means by which the immune response can be harnessed to control cancer. Our team of biomedical and clinical scientists have a strong focus in translating basic science knowledge into new therapies that can be taken to clinical trial.
Bone marrow transplantation is the most established form of cancer immunotherapy and has been a longstanding interest of our lab. Its curative potentialresides in the donor T cells, which are very effective in recognising and eradicating cancer cells. However, these T cells can also attack vital tissues, and the resulting organ damage. known as graft-versus-host disease (GVHD), is a major source of transplant-related morbidity and mortality. Our research seeks to enhance the anti-tumour response and attenuate GVHD through T cell engineering. These include the use of "safety switches" to enable T cells to be deleted in the setting of GVHD and the use of regulatory T cells (Tregs) to attenuate GVHD.
Our above experience in T cell engineering has led to our current research focus in Chimeric Antigen Receptor (CAR) T cell therapy. CAR T cells are gene-modified immune cells (T cells) that can recognise specific surface proteins on tumour cells. They can be very effective in killing these tumour cells and can cure up to 50% of certain blood cancers. Our laboratory is developing new CARs with the aims of making them more effective and accessible. These include CAR T cells directed at blood cancers and childhood cancers. In collaboration with the Royal Brisbane and Women's Hospital, we are one of only a few groups in Australia with the capacity to make clinical grade CAR T cells on campus and take them to clinical trial.
Research Projects
Current Research Projects
Developing new Chimeric Antigen Receptor (CAR) T cell therapy for the treatment of cancers, including new targets and new methods to regulate CAR T cell function
Establishing a capacity to generate clinical grade CAR T cells in-house to facilitate translation into early-phase clinical trials
Understanding the impact of CAR T cell therapy on broader immune landscape, including the non-CAR T cell compartment
Funding
- National Health and Medical Research Council
- Queensland Technology Future Fund
- Royal Brisbane and Women’s Hospital Foundation
- Tour de Cure
- Cancer Council Queensland
- Children’s Hospital Foundation
Publications
Zhang P, Fleming P, Andoniou CE, Waltner OG, Bhise SS, Martins JP, McEnroe BA, Voigt V, Daly S, Kuns RD, Ekwe AP, Henden AS, Saldan A, Olver S, Varelias A, Smith C, Schmidt CR, Ensbey KS, LeggSRW, Sekiguchi T, Minnie SA, Passos Jm Gradwll M, Savitsky P, Wagenaar I, Clouston AD, Koyama M, Furlan SN, Kennedy GA, Ward ES, Degli-Esposti MA*, Hill GR*, Tey SK* (*equal contribution). IL-6-mediated endothelial injury impairs anti-viral humoral immunity. Journal of Clinical Investigation. 2024;134(7):e174184. doi: 10.1172/JCI174184
Ekwe AP, Au R, Zhang P, McEnroe BA, Tan ML, Saldan A, Henden AS, Hutchins CJ, Henderson A, Mudie K, Kerr K, Fuery M, Kennedy GA, Hill GR, Tey SK. Clinical grade multiparametric cell sorting and gene-marking of regulatory T cells. Cytotherapy. 2024 Jul;26(7):719-728. doi: 10.1016/j.jcyt.2024.02.023. Epub 2024 Mar 5. PMID: 38530690.
Zhang P, Raju J, Ullah MA, Au R, Varelias A, Gartlan KH, Olver SD, Samson LD, Sturgeon E, Zomerdijk N, Avery J, Gargett T, Brown MP, Coin LJ, Ganesamoorthy D, Hutchins C, Pratt GR, Kennedy GA, Morton AJ, Curley CI, Hill GR, Tey SK. Phase I Trial of Inducible Caspase 9 T Cells in Adult Stem Cell Transplant Demonstrates Massive Clonotypic Proliferative Potential and Long-term Persistence of Transgenic T Cells. Clin Cancer Res. 2019 Mar 15;25(6):1749-1755. doi: 10.1158/1078-0432.CCR-18-3069. Epub 2019 Feb 14.
Student Projects
Collaborators
- Professor Di Yu, Frazer Institute, The University of Queensland
- A/Prof Glen Kennedy, Royal Brisbane and Women’s Hospital
- Professor Geraldine O'Neill, University of Sydney
- Professor David Gottlieb, Westmead Hospital, Sydney