Study level
- Master of Philosophy
- Honours
Faculty/School
Faculty of Health
Topic status
We're looking for students to study this topic.
Supervisors
- Position
- Professor
- Division / Faculty
- Faculty of Health
- Position
- Adjunct Associate Professor
- Division / Faculty
- Faculty of Health
Overview
Chimeric Antigen Receptor (CAR) T cells are genetically modified immune cells that can recognise and kill cancer cells. They do so through the CAR, which recognises specific antigens expressed on cancer cells. CAR T cell therapy has emerged as an effective form of cancer immunotherapy in certain types of blood cancers and are now approved for use in patients. However, CAR T cell therapy can only benefit a very small proportion of cancer patients at present because it is very difficult to design CARs that recognise only cancer cells and not healthy cells. CAR T cells that recognise healthy cells can cause unwanted tissue damage, resulting in life-threatening complications. The discovery of new antigen targets and the development of new ways to regulate CAR T cell function in vivo will facilitate the development of safer and more broadly applicable CAR T cell therapeutics.
1. June CH, et al. CAR T cell immunotherapy for human cancer. Science. 2018;359(6382):1361-5.
2. Guedan S, et al. Engineering and Design of Chimeric Antigen Receptors. Molecular Therapy - Methods & Clinical Development. 2019;12:145-56.
3. Martinez M, Moon EK. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Frontiers in Immunology. 2019;10:128.
4. Zhang P,… 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;25(6):1749-55.
Aims
The aim of this project is to develop new types of CAR T cell therapies that can safely and effectively target other types of cancer. This is achieved by designing the CAR gene construct so that it can target a new antigen that may be specific to cancer cells and/or by creating CAR T cells that require a second molecule to “activate” it. The function of the new CARs will be determined in vitro against cancer cell lines by cytokine secretion and cytotoxicity assays.
Approaches/skills and techniques
- Cloning Chimeric Antigen Receptor (CAR) constructs (molecular biology)
- Preparing mononuclear cells by density centrifugation
- Cell culture
- In vitro gene modification using retroviral vector
- Immunological assays – multiparametric flow cytometry, cytotoxicity assay, cytokine secretion assays
Outcomes
This project will form the first stages in the development of a potentially new CAR T cell therapeutic. The outcome will be the cloning of a prototype CAR, immunological and other functional characterisation of this CAR, and determination of its suitability for further development as a potential clinical therapeutic.
Required skills and experience
Basic laboratory skills – general lab safety, knowledge of general laboratory instruments (pipetting, operation of centrifuge etc), understands basics of aseptic technique, basic immunology knowledge.