Cancer Gene Therapy

Our links with children being treated for cancer in our hospitals ensure our research is based on real life questions that come directly from the cancer ward. Doctors in the hospital’s clinical oncology service are closely following the successful use of immune-based therapies to treat cancer, in particular solid tumours that recur or are hard to treat with standard therapies. The Cancer Gene Therapy team is using gene therapy to develop an immune- based therapy to target these types of tumours.

The project takes a patient’s T cells and re-engineers them to target and kill tumour cells in much the same way that these cells can target and kill pathogens in the body. The project brings together staff of the Children’s Cancer Research Unit’s Cancer Gene Therapy Group, the Oncology Unit and the Gene Therapy Research Unit, under the umbrella of Sydney Cell and Gene Therapy on the Westmead Campus.

Following on from this group’s experience in conducting capacity to conduct a Phase I study using gene therapy to develop treatments for brain tumours, this project also aims to test the strategy in a clinical trial.

Specialised infrastructure in the form of state-of-art cleanrooms, and well-established quality systems underpinning their operations, allow for the manipulation of patient cells using gene transfer protocols for this project.

Included in the research of re-engineering T cells to attack tumour, the group are also working on the development of vectors for gene transfer into T cells, including the scale up of vector manufacture to clinical batch size, as well as function, safety and stability testing of proposed vectors for future clinical trial use.

The research team

> Dr Geoffrey McCowage, Cancer Gene Therapy Group Leader

Geoff is a Paediatric Oncologist at The Children's Hospital at Westmead and a member of Sydney Cell and Gene Therapy (SCGT). He is a Principal Investigator for clinical trials within the Children's Oncology Group. He has a particular clinical interest in neuro-oncology and sarcomas of bone and soft tissue. Dr McCowage leads the clinical and translational research of the Cancer Gene Therapy group.

> Dr Belinda Kramer, Cancer Gene Therapy Group Co-Leader, email: belinda.kramer@health.nsw.gov.au

Belinda is a senior research scientist and leads laboratory research within the Cancer Gene Therapy Group. She is also a member of Sydney Cell and Gene Therapy (SCGT) and highly experienced in gene transfer techniques and cell therapies.

> Dr Kenneth Hsu, Senior Post-doctoral Research Officer, Cancer Gene Therapy Group Co-Leader, email: kenneth.hsu@health.nsw.gov.au

Ken is an experienced post-doctoral scientist working on the development of novel vectors for gene modification of T cells to target tumours and the development of clinically applicable T cell manufacturing methodology for the project.

> Other Research Team Members

  • Ms Shiloh Middlemiss, Research Assistant

Key publications

Clinical Trial of MGMT(P140K) Gene Therapy in the Treatment of Pediatric Patients with Brain Tumors. Kramer B, Singh R, Wischusen J, Rush A, Middlemiss S, Ching YW, Alexander IE, McCowage G. (2018) Human Gene Therapy. (Ahead of print)

Coherence analysis discriminates between retroviral integration patterns in CD34(+) cells transduced under differing clinical trial conditions. Hallwirth CV, Garg G, Peters TJ, Kramer BA, Malani NV, Hyman J, Ruan X, Ginn SL, Hetherington NA, Veeravalli L, Shahab A, Ranganathan S, Wei CL, Liddle C, Thrasher AJ, Bushman FD, Buckley MJ, Alexander IE (2015) Mol Ther Methods Clin Dev 2:15015

Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. Milne E, Greenop KR, Scott RJ, Haber M, Norris MD, Attia J, Jamieson SE, Miller M, Bower C, Bailey HD, Dawson S, McCowage GB, et al. (2015) Cancer Epidemiol Biomarkers Prev 24(1):48-56

Treatment of children with poor risk solid tumors by further escalation of the VETOPEC regimen including very high-dose cyclophosphamide and peripheral stem cell support: an Australian and New Zealand Children's Hematology and Oncology Group study. McCowage GB, et al; Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG) (2011) Pediatr Blood Cancer 2011 57(6):958-64

Methylguanine DNA methyltransferase-mediated drug resistance-based selective enrichment and engraftment of transplanted stem cells in skeletal muscle. Lee AS, Kahatapitiya P, Kramer B, Joya JE, Hook J, Liu R, Schevzov G, Alexander IE, McCowage G, et al. (2009) Stem Cells 27(5):1098-108

Characterisation of a P140K mutant O6-methylguanine-DNA-methyltransferase (MGMT)-expressing transgenic mouse line with drug-selectable bone marrow. Kramer BA, Lemckert FA, Alexander IE, Gunning PW, McCowage GB (2006) J Gene Med 8(9):1071-85