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.
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
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.
Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma (Leukemia, (2018), 32, 5, (1261-1265), 10.1038/s41375-018-0043-y) Araf S, Wang J, Korfi K et al. Leukemia (2019) 33(7) 1540
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(7) 1258-1263
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
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
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)
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)
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.