Children's Cancer Research Unit
Cancer Gene Therapy Project
Research Directions
The Children's Cancer Research Unit (CCRU) has strong links with the clinical oncology service at CHW through a series of translational research projects. The Cancer Gene Therapy project has arisen out of a clinical need to address the significant problem of the toxic side effects of chemotherapy on the bone marrow of children with brain tumours. The project, initiated by Dr Geoffrey McCowage in the Oncology Unit, is aiming to apply a gene therapy strategy, using a DNA repair protein, Methyl-Guanine-Methyl-transferase (MGMT), to provide protection to the bone marrow of these children.
Translation of laboratory based pre-clinical research of this nature demands a collaborative approach, due to the complex and varied tasks that need to be achieved. The team involved in bringing this project to fruition is made up of not only the CCRU Cancer Gene Therapy Group staff but also staff of the Oncology Unit and the Gene Therapy Research Unit at CHW. This collectively brings together:
- clinicians with expertise in oncology, bone marrow transplantation and gene therapy
- scientists experienced in the manipulation of bone marrow stem cells, gene transfer and the methods to analyse and monitor gene transfer outcomes
- administrative skills of project managers and a quality officer to oversee the regulatory and quality aspects of carrying out gene therapy in a clinical setting.
Some members of the team, under the direction of Dr Ian Alexander, Head, Gene Therapy Research Unit, gained valuable experience in clinical gene therapy trials through collaboration with Professor Alain Fischer in Paris to treat infants with a rare immune deficiency disorder known as SCID-X1.
The recent commissioning of the Westfield Gene and Cell Medicine Facility at the Hospital has provided the opportunity to build on this experience. Access is now available to state-of-the-art cleanroom facilities suitable for both the manufacture of clinical grade gene transfer reagents and the manipulation of patient cells for the gene transfer protocol.
The project is nearing the stage where a Phase I clinical trial can be initiated.
Group leader profile
Dr Geoffrey McCowage is a Senior Staff Specialist paediatric oncologist at The Children's Hospital at Westmead. He completed his medical degree at the University of Sydney and then paediatric specialist training at Sydney Children's Hospital, becoming a Fellow of the Royal Australasian College of Physicians in 1993. From 1993-1996 Dr McCowage completed a fellowship in paediatric oncology at Sydney Children's Hospital and a fellowship at Duke Medical Center in North Carolina. At Duke he took particular interest in paediatric neuro-oncology and in umbilical cord blood biology and transplantation. He undertook laboratory research in the area of gene transfer into umbilical cord blood stem cells in the laboratories of Dr Eli Gilboa and Dr Joanne Kurtzberg. In 1996 Dr McCowage took up the position of staff specialist in paediatric oncology at The Children's Hospital at Westmead. He undertakes laboratory research in gene transfer with haematopoietic stem cells, focussing on the development of clinical gene therapy trials. He is the Hospital's Principal Investigator for the clinical trials of the Children's Oncology Group as well as participating in clinical trials sponsored by industry and other consortia. He has a particular clinical interest in neuro-oncology and sarcomas of bone and soft tissue.
Funding / financial support
The principal sponsor of the Cancer Gene Therapy Group is the Oncology Children's Foundation.
Recent selected publications
Ginn SL, Curtin JA, Kramer B, Smyth CM, Wong M, Kakakios A, McCowage GB, Watson D, Alexander SI, Latham M, Cunningham SC, Zheng M, Hobson L, Rowe PB, Fischer A, Cavassana-Clavo M, Hacein-Bey_Abina S, Alexander IE. (2005) Treatment of an infant with X-linked severe Combined Immunodeficiency (SCID-X1) by gene therapy in Australia. Med. J Aust. 182 (9): 458-63.
Kramer BA, Lemckert FA, Alexander IE, Gunning PW, McCowage GB. (2006). Characterisation of a P140K mutant O(6)-methylguanine-DNA-methyltransferase (MGMT)-expressing transgenic mouse line with drug-selectable bone marrow. J Gene Med 8(9): 1071-85.
Ziegler DS, Cohn RJ, McCowage G, Alvaro F, Oswald C, Mrongovius R, White L. Australian and New Zealand Children's Study Group. Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors. Neuro-Oncology 2006; 8(1):53-9.
Ziegler DS, McCowage G, Cohn RJ, White L. Long-term survival following a phase I/II trial with VETOPEC for solid tumors in childhood. Journal of Pediatric Hematology/Oncology 2006; 28(1):40-2.
Gardner SL, Asgharzadeh S, Green A, Horn B, McCowage G, Finlay J. Intensive induction chemotherapy followed by high dose chemotherapy with autologous hematopoietic progenitor cell rescue in young children newly diagnosed with central nervous system atypical teratoid rhabdoid tumors. Pediatric Blood & Cancer. 51(2):235-40, 2008 Aug.
Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, McCowage GB, Diez B, Allen JC, Gopalan A, Cornelius AS, Termuhlen A, Abromowitch M, Sposto R, Finlay JL. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols. [Journal Article. Multicenter Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't] Pediatric Blood & Cancer. 50(6):1169-75, 2008 Jun.
This document was updated on Tuesday, 17 November 2009
| 
