Dendritic Cell Biology and Therapeutics

Dendritic Cells (DC) are unique subsets of white blood cells found throughout the body. They are responsible for initiating and directing immune responses. As one of the pioneering groups in the field, we are continuing to define the human DC subsets and elaborate their function. We aim to learn how DC interact with their environment by studying DC surface molecules and how these molecules influence DC function. Our DC knowledge is then used to benefit patients, by developing new diagnostic and potential therapeutic antibodies, which we test in preclinical models of haematopoietic stem cell transplantation, leukemia, multiple myeloma and other malignancies. Our group has completed a trial of therapeutic DC vaccination in prostate cancer and is evolving further trials of immune therapies in multiple myeloma and other malignancies. We are also developing a CD83 antibody as a novel immunosuppressive agent, which preserves the patient’s ability to fight infections and cancer for clinical trial in allogeneic transplantation.

We want to use our knowledge of DC to develop new diagnostic and therapeutic products.  We predict that the ability to analyse DC subsets and their functional status will provide diagnostic information relevant to managing the beneficial and harmful effects of the immune response in cancer, transplantation, autoimmune/inflammatory diseases and vaccinations against the major infectous diseases.  Finally, we are now looking to develop new DC based therapeutics in world first clinical trials in our new Sydney home will be ideal for this work.

Highlights

• Participation in the Human Cell Differentiation Antigen Workshop and recent involvement in an international publication on DC nomenclature has highlighted the interest in the DC field.
• Our previous work has led to the recent publication defining a new human blood CD141 DC subset (J Exp Med 2010; 207:1247).
• Our ongoing collaborative work with Brisbane colleagues has created new fully human antibodies to CD83 that immunosuppress immune responses (J Exp Med 2009; 206:387).

 Areas of Research

• Studies on DC in multiple myeloma and haematopoietic stem cell transplantation are underway via our collaborations at the Royal Prince Alfred and Westmead Hospitals.
• We have a novel DC cell surface molecule discovery project.
• Exciting new studies on the function of DC molecules in gene deleted mice will commence when the mice are transferred from Brisbane.
• Our pioneering studies using novel anti CD83 DC agents for immunosuppression will continue and move to clinical application based upon anticipated CRC-BT funding.