Translational Oncology Laboratory

Research Program Overview

In the Translational Oncology Laboratory, we are developing innovative new therapies for cancers including pancreatic and lung cancer, as well as novel approaches to better guide the use of existing therapies. We have a clear focus on the translation of our research to the clinic, enabling our discoveries to contribute to better patient outcomes as soon as possible. Much of our research is collaborative, working in close association with the Cancer Clinical Trials Unit at the Royal Adelaide Hospital, and partnering with other clinical sites, research laboratories and industry partners around Australia and internationally.

There are two major research streams within the program: one focussed on T cell-based cancer immunotherapies, and the other on antibody-targeted diagnostics and therapeutics.

Antibody Targeting

This team uses functionalised monoclonal antibodies, including antibody-drug conjugates (ADCs) and antibodies labelled with radioactive isotopes, to target tumour cells for therapeutic and diagnostic purposes.

T Cell Immunotherapies

Researchers in this team focus on novel therapies that enhance a cancer patient’s immune system, to enable the patient’s own T cells to attack their cancer. Please refer to the Cancer Immunotherapy Group page for more detail.

Current Research Projects

First-line therapy for lung cancer typically involves cytotoxic chemotherapy, which is DNA-damaging and causes cancer cell death. We have preclinical proof of concept for a novel method of detecting cancer cell death using the APOMAB® monoclonal antibody that is specific for the essential La ribonucleoprotein overexpressed in malignancy.

We are currently investigating the following applications of APOMAB®:

Antibody-drug conjugates (ADC) for bystander treatment of lung cancer: We are investigating ADC versions of APOMAB based on the premise that APOMAB-ADC-bound dead tumour cells are processed by both viable tumour cells and supporting leucocytes to produce bystander killing.
Preclinical development of an imaging agent for detection of cancer cell death: We are adapting the APOMAB® monoclonal antibody for use in immuno-positron emission tomography (PET). Non-invasive methods for detecting cancer cell death can be useful for the early evaluation of therapeutic responses
Using ADCs to stimulate anti-tumour immune responses in models of cancer: We are using ADCs alone and in combination with immunotherapy agents to both directly kill tumour cells and to modulate the body’s immune system to target and eliminate any remaining resistant cancer cells more effectively.

Laboratory staff

Laboratory head

Prof Michael Brown
+61 8 7074 2335
michaelp.brown@sa.gov.au

Independent Group Leader

Associate Professor Lisa Ebert
Cancer Immunotherapy Group

Team Members

Senior Research Fellows

Dr Alex Staudacher

Postdoctoral Research Scientists

Dr Vasilios (Bill) Liapis
Dr Nicole Wittwer

Students

Ali Nazarizadeh
Abbey Marshall

Select Recent Publications

Staudacher, A.H.*, Li, Y.*, Liapis, V. and Brown, M.P. (2022) The RNA-binding protein La/SSB associates with radiation-induced DNA double-strand breaks in lung cancer cell lines. Cancer Reports. Aug;5(8):e1543. doi: 10.1002/cnr2.1543. (*shared first authorship).
Reid, P., Staudacher, A.H., Marcu, L.G., Olver, I., Moghaddasi, L., Brown, M.P., and Bezak, E. (2021). Characteristic differences in radiation-induced DNA damage response in HPV negative and HPV positive head and neck cancers with accumulation of fractional radiation dose. Head and Neck 46:10: 3086-3096
Liapis, V., Tieu, W., Wittwer, N.L., Gargett, T., Evdokiou, A., Takhar, P., Rudd, S.E., Donnelly, P.S., Brown M.P. and Staudacher, A.H. (2021). Positron Emission Tomographic imaging of tumor cell death using Zirconium-89-labeled chimeric DAB4 following cisplatin chemotherapy in lung and ovarian cancer xenograft models. Molecular Imaging and Biology, https://doi.org/10.1007/s11307-021-01640-x
El Khawanky N, Hughes A, Yu W, Taromi S, Aumann K, Vinnakota MK, Clarson J, Lopez A, Brown MP, Duyster J, Hughes TP, White DL, Yong ASM, Zeiser R. Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia. Nat Comms 12(1), 6436, 2021.
Liapis, V., Tieu, W., Rudd, S.E., Donnelly, P.S., Wittwer, N.L., Brown M.P. and Staudacher, A.H. (2020). Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®. EJNMMI Radiopharmacy and Chemistry 5(27)
Staudacher, A.H.*, Liapis, V.*, Tieu, W., Wittwer, N.L. and Brown M.P. (2020). Tumour-associated macrophages process drug and radio-conjugates of the dead tumour cell targeting APOMAB antibody. Journal of Controlled Release 327(10): 779-787, (*both authors contributed equally)
Reid, P., Staudacher, A.H., Marcu, L.G., Olver, I., Moghaddasi, L., Brown, M.P., Li., Y. and Bezak, E. (2020). Intrinsic Radiosensitivity is not the determining factor in treatment response differences between HPV negative and HPV positive head and neck cancers. Cells 9(8):1788
Reid, P., Staudacher, A.H., Marcu, L.G., Olver, I., Moghaddasi, L., Brown, M.P. and Bezak, E. (2020). Influence of the human papillomavirus on the radio-responsiveness of cancer stem cells in head and neck cancer. Scientific Reports 10:2716
Reid, P., Marcu, L.G., Olver, I., Moghaddasi, L., Staudacher, A.H., and Bezak, E. (2019) Diversity of cancer stem cells in head and neck carcinomas: the role of HPV in cancer stem cell heterogeneity, plasticity and treatment response. Radiotherapy and Oncology 135:1-12.
Staudacher, A.H., Li, Y., Liapis, V., Hou, J., Chin, D., Dolezal, O., Adams, T.E., van Berkel, P.H. and Brown M.P. (2019). APOMAB® antibody drug conjugates targeting dead tumor cells are effective in vivo. Molecular Cancer Therapeutics 18(2): 335-345.
Staudacher, A.H., Liapis, V. and Brown M.P. (2018). Therapeutic targeting of tumor hypoxia and necrosis with antibody α-radioconjugates. Antibody Therapeutics 1:2 75-83.
Reid, P., Puthenparampil, W, Li, Y., Marcu, L.G., Staudacher, A.H., Brown, M.P. and Bezak, E. (2018). Experimental investigation of radiobiology in head and neck cancer cell lines as a function of HPV status, by MTT assay. Scientific Reports 8:7744
Staudacher, A.H. and Brown M.P. (2017). Antibody drug conjugates and bystander killing – is antigen-dependent internalization required? British Journal of Cancer 117: 1736-1742.
Reid, P., Puthenparampil, W, Li, Y., Marcu, L.G., Staudacher, A.H., Brown, M.P. and Bezak, E. (2017). In vitro investigation of head and neck cancer stem cell proportions and their changes following X-ray irradiation as a function of HPV status. PLOS One. 12(10):e0186186. doi: 10.1371/journal.pone.0186186.