PhD in Antibody Therapeutics and Targeted Cancer Therapy
Supervisor: A/Prof Daniel Christ
Our laboratory is working on the development of new antibody therapeutics.
1. Molecular Engineering of Antibody Therapeutics: Therapeutic monoclonal antibodies are among the fastest growing class of drugs in the pharmaceutical sector with more than $30 billion sales in 2012. Examples include the breast cancer drug Herceptin and the anti-inflammatory drug Humira. Unfortunately, many human antibodies display poor stability and a tendency to aggregate. This greatly hinders the development of therapeutics and results in high failure rates in pre-clinical drug development. Our group has pioneered approaches to increase the stability of human antibody therapeutics using high-throughput phage display and X-ray crystallography methods.
2. Targeted Cancer Therapy: Monoclonal antibodies hold great promise for the treatment of cancer. Unfortunately, the majority of current antibody drugs are directed against a limited number of well characterized cell surface receptors (such as HER2, EGFR). New targets and therapeutics are urgently required. Our group is developing new antibody therapeutics against targets emerging from the Garvan research programs.
Dudgeon K, Rouet R, Kokmeijer I, Schofield P, Stolp J, Langley D, Stock D and Christ D. (2012) General strategy for the generation of human antibody variable domains with increased aggregation resistance.Proc Natl Acad Sci U S A. 109: 10879-10884. [ Editorial: http://www.pnas.org/content/109/27/10741.full.pdf ]
Rouet R, Dudgeon K, Schofield P, Lowe D, Jermutus L and Christ D. (2012) Expression of high affinity antibody fragments in bacteria. Nature Protoc. 7: 364-373.
Lowe D, Dudgeon K, Rouet R, Schofield P, Jermutus L and Christ D. (2012) Aggregation, stability, and formulation of human antibody therapeutics. Adv Protein Chem Struct Biol 2011;84:1-206
O'Toole SA, Machalek DA, Shearer RF, Millar EK, Nair R, Schofield P, McLeod D, Cooper CL, McNeil CM, McFarland A, Nguyen A, Ormandy CJ, Qiu MR, Rabinovich B, Martelotto LG, Vu D, Hannigan GE, Musgrove EA, Christ D, Sutherland RL, Watkins DN, Swarbrick A. (2011) Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer. Cancer Res 71(11):4002-4014=