CASE STUDY 3
PROJECT GRANT CATEGORY
Dr Kristen Radford, Team Leader, Cancer Immunotherapies Group, Mater Research Institute.
ASSOCIATE PROFESSOR KRISTEN RADFORD 2011-2013 Project title: Targeted delivery of prostate cancer antigens to dendritic cells for immunotherapy. Immunotherapies such as the FDA approved Sipuleucil-T vaccine are promising treatments for prostate cancer. This approach currently relies on extracting blood cells from the patient and delivering cancer proteins to them in the test tube before reinfusing them into the patient, where they stimulate the body’s own immune system to attack the cancer. However, this is costly, labour intensive and not suitable or effective for many patients. Kristen and her team aim to develop a novel vaccine concept that will overcome these limitations. A/Prof Radford (Mater Research) and Dr Lahoud (Burnet Institute) have identified the rare type of blood cell in humans believed to be most effective at fighting cancer, and a novel marker specific to these cells. They are exploiting the novel marker on these cells to construct a vaccine that will deliver their new prostate cancer protein directly to them without needing to remove them from the patient.
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Knowledge and discovery The vaccine is based on the team’s three key discoveries. Firstly, they showed that rare human blood cells, called CD141+ dendritic cells, possess the desirable characteristics for mounting effective anti-cancer immune responses. Secondly, they discovered a novel marker called CLEC9A, that is specifically expressed on these cells. Thirdly, they discovered that a prostate cancer protein called kallikrein 4 is a promising target to stimulate anti-cancer immune responses. Their new vaccine will consist of the immune-stimulatory components of kallikrein 4 and other known prostate cancer immune targets. These are fused to an antibody that specifically binds to CLEC9A. So far Kristen and her team have generated a panel of the prostate cancer immune targets that are fused to the CLEC9A-specific antibody, and confirmed that these still bind CLEC9A effectively. These will be compared to antibodies that do not bind dendritic cells and to antibodies that bind all dendritic cells, to confirm their specificity and establish whether there is a selective advantage to delivering the cancer targets only to CD141+ DC. The CD141+ dendritic cells are rare, expensive and difficult to isolate and there are no in vitro culture models to study them. They have therefore developed a novel preclinical model that can be used to generate human CD141+ dendritic cells in mice that lack their own functional immune system. They have shown that these