Experimental Paediatric Oncology

Principal Investigator, Prof John Anderson

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

Funders

GOSH
CRUK
Olivia Hodson Cancer Fund
European Science Foundation
Entertainment Industry Foundation
Little Princess Trust
Children with Cancer UK
Solving Kids Cancer UK
Action Medical Research
MRC

Recent Publications

2023

Anderson J, Barisa M. (2023). Enhancing the effectiveness of γδ T cells by mRNA transfection of chimeric antigen receptors or bispecific T cell engagers. Molecular Therapy – Oncolytics, doi: 10.1016/J.OMTO.2023.08.003

Waterhouse DJ, Privitera L, Anderson J...(2023). Enhancing intraoperative tumor delineation with multispectral short-wave infrared fluorescence imaging and machine learning. Journal of Biomedical Optics, doi: 10.1117/1.JBO.28.9.094804

Privitera L, Waterhouse DJ, Preziosi A...(2023). Short-wave infrared imaging enables high-contrast fluorescence-guided surgery in neuroblastoma.Cancer Research, doi:10.1158/0008-5472.CAN-22-2918

Vydra J, Cosimo E, Lesný P…(2023). A Phase I Trial of Allogeneic γδ T Lymphocytes From Haploidentical Donors in Patients With Refractory or Relapsed Acute Myeloid Leukemia. Clinical Lymphoma, Myeloma & Leukemia, doi:10.1016/J.CLML.2023.02.003

2022

Hont AB, Dumont B, Sutton KS...(2022). The tumor microenvironment and immune targeting therapy in pediatric renal tumors. Pediatric Blood & Cancer, doi:10.1002/PBC.30110

Halliwell E, Vitali A, Muller H...(2022). Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells. Cytotherapy, doi:10.1016/J.JCYT.2022.10.007

Birley K, Leboreiro-Babe C, Rota EM...(2022). A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers. Molecular Therapy, doi: 10.1016/J.OMTO.2022.08.008

Berlak M, Tucker E, Dorel M...(2022). Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.Molecular Cancer, doi:10.1186/S12943-022-01583-Z

Ferry GM, Agbuduwe C, Forrester M...(2022). A Simple and Robust Single-Step Method for CAR-Vδ1 γδT Cell Expansion and Transduction for Cancer Immunotherapy. Frontiers in Immunology, doi:10.3389/FIMMU.2022.863155

2021

Coorens TH, Collord G, Lu W, Mitchell E, Ijaz J, Roberts T, Oliver TR, Burke A, Gattens M, Dickens E, ... Anderson J, ... Behjati, S. (2021). Clonal hematopoiesis and therapy-related myeloid neoplasms following neuroblastoma treatment.. Blood, doi:10.1182/blood.2020010150

Kildisiute, G., Kholosy, W.M., Young, M.D., Roberts, K., Elmentaite, R., van Hooff, S.R., Pacyna, CN., Khabirova, E., Piapi, A., ...Anderson, J., ...Behjati, S. (2021). Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell.. Sci Adv, 7 (6), doi:10.1126/sciadv.abd3311

2020

Pearson, A.D.J., Rossig, C., Lesa, G., Diede, S.J., Weiner, S., Anderson, J., Gray J, Geoerger, B., Minard-Colin, V., ...Vassal, G. (2020). ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients.. Eur J Cancer, 127 52-66. doi:10.1016/j.ejca.2019.12.029

Straathof, K., Flutter, B., Wallace, R., Jain, N., Loka, T., Depani, S., Wright, G., Thomas, S., Cheung, GW-K., ...Anderson, J. (2020). Anti-tumor activity without on-target off-tumor toxicity of GD2-Chimeric Antigen Receptor T cells in patients with neuroblastoma. Science Translational Medicine, doi:10.1126/scitranslmed.abd6169

Gavriil, A., Barisa, M., Halliwell, E., Anderson, J. (2020). Engineering solutions for mitigation of chimeric antigen receptor T-cell dysfunction. Cancers, 12 (8), 1-24. doi:10.3390/cancers12082326

Paraboschi, I., De Coppi, P., Stoyanov, D., Anderson, J., Giuliani, S. (2020). Fluorescence imaging in pediatric surgery: State-of-the-art and future perspectives.. J Pediatr Surg, doi:10.1016/j.jpedsurg.2020.08.004

Coorens, THH., Farndon, SJ., Mitchell, TJ., Jain, N., Lee, S., Hubank, M., Sebire, N., Anderson, J., Behjati, S. (2020). Lineage-independent tumors in bilateral neuroblastoma. New England Journal of Medicine, 383 (19), 1860-1865. doi:10.1056/NEJMoa2000962

Zormpas-Petridis, K., Poon, E., Clarke, M., Jerome, N.P., Boult, J.K.R., Blackledge, M.D., Carceller, F., Koers, A., Barone, G., ...Anderson, J., ...Jamin, Y. (2020). Noninvasive MRI native T1 mapping detects response to MYCN-targeted therapies in the Th-MYCN model of neuroblastoma.. Cancer Research, doi:10.1158/0008-5472.CAN-20-0133

Grabovska, Y., Mackay, A., O'Hare, P., Crosier, S., Finetti, M., Schwalbe, E.C., Pickles, JC., Fairchild, AR., Avery, A., ...Anderson, J., ...Williamson, D. (2020). Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity.. Nat Commun, 11 (1), 4324. doi:10.1038/s41467-020-18070-y

2019

George, S.L., Izquierdo, E., Campbell, J., Koutroumanidou, E., Proszek, P., Jamal, S., Hughes, D., Yuan, L., Marshall, LV., ...Anderson, J., ... Chesler L. (2019). A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations. European Journal of Cancer, doi:10.1016/j.ejca.2019.07.027

Coorens, T.H.H., Treger, T.D., Al-Saadi, R., Moore, L., Tran, M.G.B., Mitchell, T.J., Tugnait, S., Thevanesan, C., Young, MD., ...Anderson, J., ...Behjati S. (2019). Embryonal precursors of Wilms tumor.. Science, 366 (6470), 1247-1251. doi:10.1126/science.aax1323

Nieddu, V., Piredda, R., Bexell, D., Barton, J., Anderson, J., Sebire, N., Kolluri, K., Janes, SM., Karteris, E., Sala, A. (2019). Engineered human mesenchymal stem cells for neuroblastoma therapeutics. Oncology Reports, doi:10.3892/or.2019.7152

Fisher, J., Sharma, R., Don, D.W., Barisa, M., Hurtado, M.O., Abramowski, P., Porter, L., Day, W., Borea, R., Inglott, S., Anderson, J., Pe'er, D. (2019). Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors.. Sci Signal, 12 (598), doi:10.1126/scisignal.aax1872

Barton, J., Pacey, K., Jain, N., Kasia, T., Edwards, D., Thevanesan, C.,Straathof, K., Barone, G., Anderson, J. (2019). Establishment and phenotyping of neurosphere cultures from primary neuroblastoma samples.. F1000Res, 8 823. doi:10.12688/f1000research.18209.1

Mahamdallie, S., Yost, S., Poyastro-Pearson, E., Holt, E., Zachariou, A., Seal, S., Elliott, A., Clarke, M., Warren-Perry, M., ...Anderson, J., ...Rahman, N. (2019). Identification of new Wilms tumour predisposition genes: an exome sequencing study.. Lancet Child Adolesc Health, doi:10.1016/S2352-4642(19)30018-5

Jain, N., Halbert, J., Patel, P.A., Biassoni, L., Anderson, J., Sebire, N., McHugh, K., Barone, G. (2019). Importance of Magnetic Resonance Imaging With Diffusion-weighted Imaging in Guiding Biopsy of Nodular Ganglioneuroblastoma: A Case Report.. J Pediatr Hematol Oncol, doi:10.1097/MPH.0000000000001686

Yogev, O., Almeida, G.S., Barker, K.T., George, S.L., Kwok, C., Campbell, J., Zarowiecki, M., Kleftogiannis, D., Smith, LM., ...Anderson, J., ...Chesler, L. (2019). In vivo modelling of chemo-resistant neuroblastoma provides new insights into chemo-refractory disease and metastasis. Cancer Research, doi:10.1158/0008-5472.CAN-18-2759

Zormpas-Petridis, K., Jerome, N.P., Blackledge, M.D., Carceller, F., Poon, E., Clarke, M., McErlean, CM., Barone, G., Koers, A., ...Anderson, J., ...Jamin, Y. (2019). MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment. Cancer Research, doi:10.1158/0008-5472.CAN-18-3412

Youssef, G., Gillett, C., Rampling, D., Chagtai, T., Virasami, A., Barton, J., Edwards, D., Sebire, N., Anderson, J., Montano, X. (2019). The presence of Y674/Y675 phosphorylated NTRK1 via TP53 repression of PTPN6 expression as a potential prognostic marker in neuroblastoma.. Hum Pathol, doi:10.1016/j.humpath.2018.12.003

Ollé Hurtado, M., Wolbert, J., Fisher, J., Flutter, B., Stafford, S., Barton, J., Jain, N., Barone, G., Majani, Y., Anderson, J. (2019). Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function.. PLoS One, 14 (8), e0216373. doi:10.1371/journal.pone.0216373

2018

Birley, K., Chester, K., Anderson, J. (2018). Antibody based therapy for childhood solid cancers. Current Opinion in Chemical Engineering, 19 153-162. doi:10.1016/j.coche.2018.01.005

Fisher, J., Anderson, J. (2018). Engineering Approaches in Human Gamma Delta T Cells for Cancer Immunotherapy. FRONTIERS IN IMMUNOLOGY, 9 doi:10.3389/fimmu.2018.01409

Wegert, J., Vokuhl, C., Collord, G., Velasco-Herrera, MDC., Farndon, SJ., Guzzo, C., Jorgensen, M., Anderson, J., Slater, O., ...Behjati, S. (2018). Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants. NATURE COMMUNICATIONS, 9 doi:10.1038/s41467-018-04650-6

Group members

Dr Marta Barisa
Senior Research Associate
m.barisa@ucl.ac.uk
UCL Profiles page: Marta Barisa

Ms Courtney Himsworth
Research Assistant
c.himsworth@ucl.ac.uk
UCL Profiles page: Courtney Himsworth

Miss Farah Alam
PhD student
farah.alam.20@ucl.ac.uk
UCL Profiles page: Farah Alam

Miss Gabrielle Ferry
Research Fellow
gabrielle.ferry.18@ucl.ac.uk
UCL Profiles page: G abrielle Ferry

Ms Henrike Muller
PhD student
henrike.muller.16@ucl.ac.uk
UCL Profiles page: Henrike Muller

Ms Marilena Nicolaidou
Research Technician
m.nicolaidou@ucl.ac.uk

Miss Meshael Artuki
PhD student
meshael.alturki.19@ucl.ac.uk
UCL Profiles page: Meshael Artuki

Dr Sonia Morlando
Research Fellow
s.morlando@ucl.ac.uk

Ms Sophie Munnings-Tomes
Research Assistant
s.munnings-tomes@ucl.ac.uk

Previous Lab Members:

Kathleen Birley
Emma Halliwell
Beth Hawkins
Kristen Koopmans
Neha Jane
Artemis Gavriil
Irene Paraboschi
Laura Privitera
Charles Agbuduwe
Carla Bautista
Jennifer Frosch
Nisansala Wisidagamage Don
Alice Vitali
Ilia Leontari
Clara Leboreiro Babe