Advanced Cellular Therapeutics (ACT)

Cellular therapies hold great promise for treating some of the most difficult to treat children’s cancer. There has been much success in the use of cellular therapies in the treatment of some blood cancers, but the application of this therapy to treatment of solid cancers is lagging. We aim to develop cellular therapies to treat solid cancers and brain cancers of childhood. Our approaches include re-engineering immune cells from the patient’s blood to attack the cancer cells, development of vectors for gene transfer into patient immune cells and 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, Advanced Cellular Therapeutics 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, Advanced Cellular Therapeutics Group Co-Leader, email:

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.

> Other Research Team Members

  • Mr Bryce Thomas, Research Assistant
  • Dr Kenneth Hsu, Senior Post-doctoral Research Officer

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