Experimental Paediatric Oncology

Biography

I was appointed as a Clinical Lecturer in paediatric oncology at UCL Great Ormond Street Institute of Child Health (GOS-ICH) in 1998 after completing my PhD in cancer biology, undertaken as a clinical research fellow at the Institute of Cancer Research (1995-1998). My initial 4 year appointment (1998-2002) at GOS-ICH was funded by a donation to ICH from the Great Ormond Street Hospital Special Trustees. In 2001 I was awarded a Cancer Research UK (then the Cancer Research Campaign) Clinician Scientist Fellowship (2002-2007). Since 2007, I have received HEFCE and Great Ormond Street Biomedical Research Centre core funding. In 2005 I gained Certificate of Completion of Specialist Training in Paediatrics and Paediatric Oncology and was appointed as Honorary Consultant Oncologist at Great Ormond Street Hospital.

Research

In 2004, using what was then new the new exciting technology of expression microarrays, we discovered that a gene fusion in aggressive childhood sarcoma called PAX3-FOXO1, confers on tumour cells the ability to avoid detection by the immune system. Since then the research from our group has focussed on identifying ways to overcome immune-suppression and develop effective immunotherapies in childhood solid cancers. Having discovered (2005-2010) that vaccine-type approaches to target candidate childhood solid cancer antigens, generated in general only low affinity and ineffective T cell receptor responses, our research focus shifted to cellular therapies using engineered T cells of both conventional and gamma-delta varieties. Our current focus is on the generation of chimeric receptors for transduction of T cells using novel antibodies with a high degree of specificity for children’s solid cancers, and with particular interest in fine-tuning of signaling through engineering and drug combination strategies. We were recently awarded approximately £9m in research clinical trial grant funding to take two of these products to phase I clinical trial testing.

Currently the group is in receipt of around £15m in competitive grant funding from research councils and charities. The work has predominant translational focus whereby clinical observation is used to identify research priorities and opportunities, and the availability of patient populations allows the rapid introduction of innovative treatments in clinical trials. Observations from experimental medicine are also used to generate novel hypothesis to test in the laboratory. The programme encompasses the full translational spectrum from gene discovery, viral and transgene engineering, development and refinement of in vivo models for experimental combination therapeutics, biomarker and imaging development, and GMP implementation.

Collaboration is at the heart of all activity which is reflected in the many partnerships and shared grants with national and international lead resaerchers in the childhood oncology field. Notable grants are the Stand up to Cancer/ CRUK Paediatric Cancer New Discoveries Challenge (($5m), MRC DPFS grant (£4.2m) to deliver degrader regulated anti-B7H3 CAR-T cells to children with brain tumours, three programme grants joint with ICR and University of Newcastle to develop new combination therapies in children with medulloblastoma, and three project grants to develop switchable CARs using degrader chemistry. Recently we led a shortlisted workpackage for development of degrader regulated CAR-T cells in the latest round of CRUK Cancer Grand Challenges.

UCL Appointments

• Professor of Experimental Paediatric Oncology
  University College London, Developmental Biology & Cancer Dept

Degrees

• Doctor of Philosophy
  University of London, 1998
• Bachelor of Medicine/Bachelor of Surgery
  University of Newcastle upon Tyne, 1991
• Bachelor of Arts - Biochemistry
  University of Oxford, 1986

Fields of Research

• Oncology and carcinogenesis
• Clinical sciences
• Immunology
• Paediatrics