Advancing CAR-T cell therapy for solid tumours in children

In Australia, about 300 children are yearly diagnosed with extracranial solid cancer, with the majority of cases made up of neuroblastoma and sarcoma. While survival rates for these diseases have increased over the past few decades, most children that relapse (20 to 30% of cases) will succumb to their disease. Moreover, survivors often suffer from life-long detrimental health effects due to current treatments that are heavily based on chemotherapeutics. With childhood cancers on the rise, there is thus an urgent need for more effective and safer therapies to prevent relapse or to treat relapsed disease. The development of effective immunotherapies that use and boost the body’s immune system to fight cancer cells, could provide a solution. Chimeric Antigen Receptor (CAR)-T cells, T-cells that have been isolated from patients and modified to attack the patient’s immune cells, have produced impressive clinical responses in childhood leukaemias, but their success in solid child tumours has been very limited. This is thought to be due to two key factors: 1) The tumour microenvironment of solid paediatric cancers is often modified by the cancer cells to be immunosuppressive, allowing cancer cells to escape both the immune system and immunotherapies such as CAR-T cells; and 2) Conventionally produced CAR-T cells suffer from suboptimal functioning.

In this project we aim to provide a solution for both these important limitations. For CAR-T cells to be effective in solid child cancers, novel strategies to enhance their functioning and long-term persistence must be combined with approaches to overcome immunosuppression. Our strategy to achieve this goal is : 1) to apply a new, clinically suitable CAR-T cell production procedure, recently developed by us, using paediatric patient blood samples to produce a novel generation of more potent CAR-T cells; and 2) to combine these superior CAR-T cells with novel anti-cancer drugs currently investigated by us, each of which inhibits tumour growth in preclinical child cancer models and rewires the immunosuppressive tumour microenvironment, in order to develop a potent combination CAR-T cell therapy that can be translated into the clinic.

How to Apply

Express your interest in this project by emailing Dr Klaartje Somers at klaartje.somers@unsw.edu.au. Include a copy of your CV and your academic transcript(s).