Congratulations to Dr Kenneth Hsu

Congratulations to our most recent Ethan Davies Fellow, Dr Kenneth Hsu, who will be inbound to the Telethon Kids Institute from the Children’s Cancer Research Unit at the Children’s Hospital at Westmead, Sydney.

While at the Institute, Dr Hsu will test a novel cellular therapy on childhood brain tumour models, based on the genetic modification of immune T cells. The data generated by Dr Hsu’s collaboration with the Institute would, if successful, support the inclusion of children with brain tumours in a planned clinical trial.

About Dr Hsu

Dr Hsu is a molecular immunologist with a solid track record in fundamental immunological research.

As a senior scientist and co-leader in the Cancer Gene Therapy team at the Children’s Hospital at Westmead, Dr Hsu’s research is focused on the clinical development of adoptive T cell therapy. His work largely involves the development and preclinical evaluation of novel viral vectors for gene modification and production modified CAR T cells to target childhood cancers.

Dr Hsu is also responsible for the development of clinically applicable large-scale delivery vectors and T cell manufacturing processes, as well as function, safety and stability testing for future clinical trial use.

The project: CAR T cell immunotherapies for children with brain tumours

Immunotherapy treatments, such as check point inhibiters and genetically modified T cells, are rapidly evolving as a new and promising form of cancer therapy at the forefront of cancer research. The focus of Dr Hsu’s work at the Cancer Gene Therapy team at the Children’s Hospital at Westmead is developing and testing immune based therapies for childhood cancers that are difficult to cure.

In particular, Dr Hsu is working on Chimeric Antigen Receptor (CAR) T cells that can target a range of proteins that are expressed in childhood cancer tumours. To date, he and his team have developed a CAR that targets the Ephrin Receptor 2A (EphA2) protein that is expressed on up to one-third of all patient tumours at the Children’s Hospital at Westmead. Already, his team has shown that EphA2 CAR T cells effectively kills both sarcoma and brain tumour cells in the lab, and shown efficacy for two bone sarcoma in vivo models. Based on these successes, Dr Hsu’s team has received funding and is preparing for a Phase I clinical trial in patients with recurrent bone sarcomas that express EphA2.

Since EphA2 is also expressed in brain tumours (including ependymoma, medulloblastoma, high grade glioma, and DIPG), the ideal Phase I study would include children with these brain cancers. Currently, there are only two early phase trials internationally (Seattle Children’s Hospital) testing CAR T cells targeting two other receptors (Her-2 and EGFR) expressed in childhood brain tumours. EphA2 CAR T represents a third target, and an important first step into the clinic to deliver these types of therapies to Australian children with brain cancer.

To include children with brain cancer in the planned trial, it will be necessary to show efficacy of EphA1 CAR
T cells in relevant in vivo brain tumour models. Dr Hsu’s own team does not have any appropriate models and it would otherwise take an extended period and be problematic due to the lack of suitable imaging technology to monitor the treatment effects during the experiment. However, the use of well-established in vivo models at the Telethon Kids Cancer Centre’s Brain Tumour Lab could explore the hypothesis that children with brain cancer should be included in the Phase I trial.

The initiation of this Phase I trial will lay the foundation to achieve a collective aim to have novel therapies available to children with cancer (hopefully including brain cancer) when current treatments fail. In the longer term, if successful, CAR T cell therapies may also prove effective for earlier stage treatment.