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Immuno-polymeric drugs for prostate cancer therapy (2016–2018)

Abstract:
Prostate cancer is the most common cancer in men over 50 and second most frequent cause of cancer deaths in Western society. There is an obvious need to develop new technologies to treat prostate cancer, leading to improved outcomes for patients and alleviating burden on the healthcare system. Importantly, such methodologies must be translatable to clinical use, and so be readily formulated and exhibit improved efficacy over current therapeutics. We hypothesise that utilisation of well-established pegylated liposomal formulations of docetaxel can be targeted to cell markers on prostate cancer using recently developed bispecific antibody formats. This approach utilises a formulation methodology that is already utilised in clinical treatments of many cancers (e.g. Doxil formulations to deliver the drug, Doxorubicin), and aims to enhance uptake of the prostate cancer drug docetaxel into prostate tumours by exploiting immune-targeting techniques. Importantly, bispecific antibodies that show high affinity for PEG on the liposome surface in addition to prostate cancer cells (e.g. prostate-specific membrane antigen or EphA2), rapidly improve ligation of the antibody and lead to significantly enhanced uptake in solid tumours, using a clinically-translatable formulation method. We will test the nanomedicine in canine patients that have been diagnosed with prostate cancer ¿¿¿ these patients exhibit cancer that is representative of the human disease. This strategy addresses a number of important problems associated with prostate cancer therapies, most notably the reduction of side-affects associated with indiscriminate toxicity of docetaxel. In addition, use of antigen interactions to chelate targeting antibodies to liposomal formulations alleviates the need for complex and often unstable chemistries. This research will ultimately provide both a fundamental understanding of nanomedicine-based therapeutics, as well as advancement towards clinical translation of the therapy.
Grant type:
NHMRC Project Grant
Researchers:

  • Professor Kristofer Thurecht

    Senior Group Leader and Deputy Dire
    Centre for Advanced Imaging
    Australian Institute for Bioengineering and Nanotechnology
    Affiliate PRF & Group Leader
    Australian Institute for Bioengineering and Nanotechnology

  • Emeritus Professor Stephen Mahler

    Emeritus Professor
    Australian Institute for Bioengineering and Nanotechnology

  • Dr Christopher Howard

    Advance Qld Industry Res Fellow
    Australian Institute for Bioengineering and Nanotechnology
Funded by:
National Health and Medical Research Council