Dr Jeff Davies

MA, MRCP, FRCPath, PhD
Reader in Haemato-oncology and Honorary Consultant
Group Leader
Research Focus

My group works on developing novel approaches to improve efficacy and safety of allogeneic stem cell transplantation and adoptive immunotherapy as treatments for blood cancers. We focus on T-cell alloreactivity in the context of stem cell transplantation and immunotherapy.

Key Publications

Infusion of alloanergized donor lymphocytes after CD34-selected haploidentical myeloablative hematopoietic stem cell transplantation. Clin Cancer Res (2018) [Epub ahead of print]. PMID: 29769208

TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses. Blood (2016) 7;128(1):72-81. PMID: 27103745

Combining CD19 Redirection and Alloanergization to Generate Tumor-Specific Human T Cells for Allogeneic Cell Therapy of B-Cell Malignancies. Cancer Research (2010) 70(10):3915-24. PMID: 20424114

Expansion of allospecific regulatory T cells after anergized, mismatched bone marrow transplantation. Science Translational Medicine (2009) 1(1):1ra3. PMID: 20368155

Major Funding
  • 2018-2021- Cancer Research UK, CRUK Clinical Award Training Cycle 4 - 2018, £512,000.00
  • 2017-2020- William Harvey Research Limited, Identifying Mechanisms of Immune Escape that leads to Relapse of Acute Myeloid Leukaemia after Allogeneic Stem Cell Transplantation, £300,000
Other Activities
  • British Society for Blood and Marrow Transplantation member
  • National Steering Committee Chair HLA-epitope matching and platelet transfusion study
  • London Cancer Pathway board for lymphoma 2015
Research

In the lab I focus on the development of novel approaches to improve efficacy and reduce toxicity of allogeneic HSCT and adoptive immunotherapy as treatments for blood cancers and other diseases.

We have a major interest in T-cell alloreactivity in the context of HSCT and immunotherapy. Current funded research projects include examination of the tissue-specific T-cell mediators of gastro-intestinal GvHD, use of new technologies to intergrate immune reconstition signatures after transplantation, epigenetic mechanism resulting in immune escape of cancer cells after transplant and limiting cancer antigen-specific T-cell responses and differential metabolism of alloreactive T cells.

I now combine my laboratory and translational research programme with clinical practice with the Cancer Centre at Barts Health, with specific emphasis on the lymphoma service and development of the allogeneic transplant/immunotherapy programmes and run a portfolio of clinical trials in GvHD. I led a successful bid in 2017 for Barts to be selected for funding as one of 10 UK transplant centres as part of a new IMPACT national HSCT clinical trials network.

Other Activities
  • British Society for Blood and Marrow Transplantation member
  • National Steering Committee Chair HLA-epitope matching and platelet transfusion study
  • London Cancer Pathway board for lymphoma 2015
Major Funding
  • 2018-2021- Cancer Research UK, CRUK Clinical Award Training Cycle 4 - 2018, £512,000.00
  • 2018-2021- CRUK Clinical Research Fellowship, Exploiting metabolic reprogramming in human allogeneic T cell responses, £230,000
  • 2017-2020- CRUK Clinical Research Fellowship, Using autoimmunity as a guide to improve cancer immunotherapy, £230,000
  • 2017-2020- William Harvey Research Limited, Identifying Mechanisms of Immune Escape that leads to Relapse of Acute Myeloid Leukaemia after Allogeneic Stem Cell Transplantation, £300,000
  • 2011-2015- Medical Research Council, Generation of suppressive donor T cells to specifically control alloresponses after allogeneic stem cell translantation, £1,450,155.00
Recent Publications

Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma. Araf S, Wang J, Korfi K et al. Leukemia (2019) 33(2) 1540
https://www.ncbi.nlm.nih.gov/pubmed/30903015

Infusion of alloanergized donor lymphocytes after CD34-selected haploidentical myeloablative hematopoietic stem cell transplantation DAVIES JK, Brennan L, Wingard J et al. Clinical Cancer Research (2018) (1)

Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma. Araf S, Wang J, Korfi K et al. Leukemia (2018) 32(2) 1261-1265
https://www.ncbi.nlm.nih.gov/pubmed/29568095

Durable graft-versus-leukaemia effects without donor lymphocyte infusions- results of a Phase II study of sequential T-replete allogeneic transplantation for high-risk acute myeloid leukaemia and myelodysplasia DAVIES JK, Hassan S, Sarker S et al. British Journal of Haematology (2017) (1)

TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses Kotsiou E, Okosun J, Besley C et al. Blood (2016) 128(1) 72-81

Allospecific Tregs expanded after anergization remain suppressive in inflammatory conditions but lack expression of gut-homing molecules. Kotsiou E, Gribben JG, Davies JK Molecular therapy : the journal of the American Society of Gene Therapy (2016) 24(1) 1126-1134

DURABLE REMISSIONS AFTER SEQUENTIAL TRANSPLANTATION USING T-REPLETE NON-MYELOABLATIVE CONDITIONING FOR RELAPSED/REFRACTORY ACUTE MYELOID LEUKAEMIA AND MYELODYSPLASIA Hassan S, Davies J, Smith M et al. HAEMATOLOGICA (2015) 100(11) 278-278
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000361204902208&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Phenotypic and functional stability of regulatory T cells expanded after alloanergization with costimulatory molecule blockade Kotsiou E, Guinan E, Gribben J et al. BONE MARROW TRANSPLANTATION (2015) 50(11) S373-S373
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000351632902120&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Lenalidomide Enhances Human Alloresponses By Increasing Proliferation of Effector Memory CD8 T Cells with Enhanced Polyfunctional Effector Capacity and a Unique Gene Expression Profile Besley CM, Kotsiou E, Petty R et al. BLOOD (2014) 124(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000349243506086&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

TNFRSF14 aberrations in Follicular Lymphoma B Cells Result in Increased Alloresponses in Vitro and in Vivo Kotsiou E, Okosun J, Clear AJ et al. BLOOD (2014) 124(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000349242702209&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

For additional publications, please click here
Team

Clinical Research Fellows
Dr Sarah Charrot, Dr Matthew Mee, Dr Symeon Theocharidis, Dr James Aries

Biography

I developed my research interest during my MRC Clinical Research Training Fellowship at the Royal Free Hospital, London, where I studied ways to selectively deplete alloreactive donor T cells to reduce GvHD but maintain immune reconstitution after allogeneic HSCT. I was awarded the George Santos Award by the American Society for Blood and Marrow Transplantation for the best clinical research by a young investigator for this research.

In 2006, I joined the Dana-Farber Cancer Institute/Harvard Medical School as a junior faculty member in Medical Oncology. I performed translational research with Profs Lee Nadler and Eva Guinan using costimulatory blockade to induce allospecific anergy in donor lymphocytes, to reduce GvHD but preserve immune reconstitution and GvL effects after allogeneic HSCT.

During that time I also gained experience in other adoptive immunotherapy approaches to cancer treatment, and I was the recipient of a Career Development Award from the Leukaemia and Lymphoma Society and a New Investigator Award from the American Society for Blood and Marrow Transplantation.

In 2010 I joined the Centre for Haemato-Oncology in the Barts Cancer Institute as a Clinical Senior Lecturer funded initially as a Clinician Scientist by the MRC.

Qualifications

  • MA (Oxon) Physiological Sciences First Class 1989
  • BM BCh (Hons) (Oxon) 1992
  • MRCP (UK) 1996
  • MRCPath 2002
  • PhD (University of London) 2005
  • FRCPath 2008