Fred Chen is a consultant haematologist with a strong interest in Stem Cell Transplantation (SCT). Fred is closely involved in clinical trials of adoptive transfer approaches involving viral-specific CD8+ T cells after SCT, to prevent acute cytomegalovirus infection.
Consultant Haematologist, Queen Elizabeth Hospital Birmingham.
Honorary Senior Lecturer, Institute of Immunology and Immunotherapy, University of Birmingham.
Head, Adoptive Cell Therapy Programme, NHSBT, Birmingham.
Background and Research focus
As a clinical haematologist, Fred has built a research programme focussing on developing cell therapy approaches to optimize haematopoietic stem cell transplantation (HSCT). HSCT can cure many patients with haematological malignancies, but major complications include risk of mortality from disease relapse, infections, and graft-versus-host disease. Fred’s research focuses on developing adoptive T cell therapy (ACT) to treat such patients, and he is involved in clinical trials of antigen-specific adoptive transfer strategies for viral infections including cytomegalovirus (e.g. the phase II trial CMV-ACE/ASPECT and the phase III trial CMV-IMPACT). He is also closely involved in immune monitoring for patients on these trials, and set up a centralized immune diagnostic facility based at Birmingham NHSBT for immune monitoring from 11 trial sites. Preclinical work is also focussing on ACT for EBV-associated malignancies, namely post-transplant lymphoproliferative disease (PTLD). As PTLD expresses EBV-derived antigens, therapeutic strategies include ACT using EBV-specific T cells derived from healthy EBV+ donors, or alternatively using T cells transduced with EBV-specific T cell receptors (TCRs). Fred hopes to translate this work, supported by NHSBT Programme funding, into a national phase II trial of EBV ACT for PTLD. Additionally, Fred and his team are investigating developing clinical protocols that use cord blood as a source of T cells with high replicative capacity for TCR-gene transfer-based ACT strategies. More recently, he has developed a research interest in rare vascular disorders of the liver that often manifest in young adults including Budd–Chiari syndrome. Fred’s research is highly collaborative, interfacing between University of Birmingham-based immunology groups (e.g. Professor Paul Moss and Dr Steve Lee) and stem cell services based at Birmingham NHSBT.
haematological malignancies; stem cell transplantation; post-transplant lymphoproliferative disorder; clinical trials; early phase clinical trial development; immune monitoring; cytomegalovirus; CMV, Epstein-Barr virus; immunotherapy strategies; JACIE accreditation.fibroblast; rheumatoid arthritis; Budd–Chiari syndrome.
Having trained in Haematology at the Hammersmith and Guy’s and St Thomas’ hospitals and King’s College, Fred has a broad interest in haematology and immunotherapy, but a particular interest in cellular immunotherapies. Following his appointment in Birmingham, he was made JACIE Medical Director of NHSBT Stem Cells and Immunotherapies, Birmingham, and also acts as regional clinical lead for stem cell services, leading the translation of novel cell therapies from bench experimentation to clinical translation. Fred also runs a monthly clinic with Dr Dhiraj Tripathi (Consultant Hepatologist) at the Centre for Rare Diseases (Heritage building QE Medical campus which offers a one stop service for patients with Budd–Chiari syndrome or other vascular liver disorders. In addition to leading his own research group, Fred sits on the CIIC Advisory Board, and also the NIHR Stem Cell Strategy Group.
Tubb VM, Schrikkema DS, Croft NP, Purcell AW, Linnemann C, Freriks MR, Chen F, Long HM, Lee SP, Bendle GM. Isolation of T cell receptors targeting recurrent neoantigens in hematological malignancies. J Immunother Cancer. 2018 Jul 13;6(1):70. doi: 10.1186/s40425-018-0386-y.
Novitzky-Basso I, Spring F, Anstee D, Tripathi D, Chen F. Erythrocytes from patients with myeloproliferative neoplasms and splanchnic venous thrombosis show greater expression of Lu/BCAM. Int J Lab Hematol. 2018 May 13. doi: 10.1111/ijlh.12838. [Epub ahead of print]
Harrison CN, Mead AJ, Panchal A, Fox S, Yap C, Gbandi E, Houlton A, Alimam S, Ewing J, Wood M, Chen F, Coppell J, Panoskaltsis N, Knapper S, Ali S, Hamblin A, Scherber R, Dueck AC, Cross NCP, Mesa R, McMullin MF. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017 Oct 26;130(17):1889-1897. doi: 10.1182/blood-2017-05-785790. Epub 2017 Aug 9.
Khan F, Rowe I, Martin B, Knox E, Johnston T, Elliot C, Lester W, Chen F, Olliff S, Mehrzad H, Zia Z, Tripathi D. Outcomes of pregnancy in patients with known Budd-Chiari syndrome. World J Hepatol. 2017 Jul 28;9(21):945-952. doi: 10.4254/wjh.v9.i21.945.
Defour JP, Hoade Y, Reuther AM, Callaway A, Ward D, Chen F, Constantinescu SN, Cross NCP. An unusual, activating insertion/deletion MPL mutant in primary myelofibrosis. Leukemia. 2017 Aug;31(8):1838-1839. doi: 10.1038/leu.2017.153. Epub 2017 May 22.
Du M, Kalia N, Frumento G, Chen F, Zhang Z. Biomechanical properties of human T cells in the process of activation based on diametric compression by micromanipulation. Med Eng Phys. 2017 Feb;40:20-27. doi: 10.1016/j.medengphy.2016.11.011. Epub 2016 Dec 9.
Raeiszadeh M, Pachnio A, Begum J, Craddock C, Moss P, Chen FE. Characterization of CMV-specific CD4+ T-cell reconstitution following stem cell transplantation through the use of HLA Class II-peptide tetramers identifies patients at high risk of recurrent CMV reactivation. Haematologica. 2015 Aug;100(8):e318-22. doi: 10.3324/haematol.2015.123687. Epub 2015 May 14.
Haldar D, Chen F, Byron J, Elsharkawy AM, Perera MT. Is it time to revisit contraindications to organ donation from donors with a JAK-2 mutation? Safe use of a liver allograft from a donor with essential thrombocythaemia. Transpl Int. 2015 Jul;28(7):881-3. doi: 10.1111/tri.12558. Epub 2015 Mar 27.
Uttenthal B, Martinez-Davila I, Ivey A, Craddock C, Chen F, Virchis A, Kottaridis P, Grimwade D, Khwaja A, Stauss H, Morris EC. Wilms’ Tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia induces short-lived WT1-specific immune responses. Br J Haematol. 2014 Feb;164(3):366-75.
Frumento G, Zheng Y, Aubert G, Raeiszadeh M, Lansdorp PM, Moss P, Lee SP, Chen FE. Cord blood T cells retain early differentiation phenotype suitable for immunotherapy after TCR gene transfer to confer EBV specificity. Am J Transplant. 2013 Jan;13(1):45-55