Professor Benjamin Willcox BA, DPhil

Benjamin Willcox

Institute of Immunology and Immunotherapy
Professor of Molecular Immunology

Contact details

Address
Birmingham CRUK Cancer Centre
Institute of Immunology and Immunotherapy

Ben Willcox is Professor of Molecular Immunology and Cancer Research UK Birmingham Centre Scientific Director based in the Institute of Immunology and Immunotherapy.

Ben leads an active research group in the field of cancer immunology and immunotherapy, with a focus on understanding immune receptor recognition. His recent work focuses on novel tumour antigens and unconventional T cell function, particularly in immunosurveillance of cellular stress. He has received major grants from Cancer Research UK, the Medical Research Council, the Biotechnology and Biological Sciences Research Council, and most recently the Wellcome Trust.

In addition, Ben is Director of the University's Cancer Immunology and Immunotherapy Centre, a collaborative grouping of over 30 academic and clinical groups focussed on understanding fundamental aspects of tumour immunology and applying these to the development of novel cancer immunotherapy strategies.

Ben is also Scientific Director of the College of Medical and Dental Sciences' (CMDS) Protein Expression Facility, a component of CMDS's Technology Hub that supports a diverse range of biomedical research across CMDS by providing high quality protein expression services. He is also a member of the Birmingham Structural Biology Consortium, a cross-college grouping of structural biology research teams.

Qualifications

  • DPhil Immunology 1999 (University of Oxford) 
  • BA (Hons) Biochemistry 1995 (University of Oxford)

Biography

Throughout his career Ben has been involved in research into the molecular basis of immune receptor recognition, a theme his research group at the University of Birmingham is focussed on.

Initial PhD studies at the University of Oxford centred on understanding protein-protein interactions critical to conventional T-cell antigen recognition. Subsequent Wellcome Trust-funded postdoctoral work in Professor Pamela Bjorkman’s US-based laboratory focussed on the Leukocyte Immunoglobulin-like Receptors (LILRs), a novel immune receptor family expressed predominantly on myeloid lineages, which play important roles in immune tolerance. Ben then returned to the UK in 2002 to establish his own independent research group at the University of Birmingham, supported by an MRC Career Development Award from 2004. He was appointed as Senior Research Fellow in 2005, and as Reader in Molecular Immunology in 2010. 

Ben's research team combines molecular, structural and cellular expertise to understand clinically important immune receptor recognition events, including those underpinning the graft-versus leukaemia effect, unconventional T cell immunosurveillance of tumours, and receptors regulating myeloid cells.

Teaching

Postgraduate supervision

Ben is interested in supervising doctoral research students in the following areas:

  • The role of gamma delta T cells in tumour immunity 
  • Immune presentation and recognition of phosphopeptide antigens

If you are interesting in studying any of these subject areas please contact Professor Benjamin Wilcox directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research Themes

Tumour Immunology and Immune/Gene Therapy, Structural Biology and Biomarkers, Cancer Cell Biology

Research Activity

My group has two active and related research areas, focussing on antigen recognition by conventional and unconventional T cells, respectively. 


Understanding T-cell recognition of novel tumour-associated antigens

Conventional T-cells make key contributions to anti-tumour immunity, by using their T-cell receptors (TCRs) to recognise tumour peptides presented in the context of MHC molecules on the tumour cell surface. Their huge potential in cancer immunotherapy is evident during stem cell transplantation treatment of haematological malignancies, where they underly the potent “graft versus leukaemia” (GvL) effect that is frequently curative. Understanding the critical receptor-ligand recognition events involved is vital if we are to effectively exploit them in cancer immunotherapy. Our approach employs both cellular techniques and molecular ones such as surface plasmon resonance and x-ray crystallography to examine the properties of key TCR/MHC interactions. Our previous studies focussed on novel tumour associated antigens (TAAs), including minor histocompatibility antigens and allo-MHC-restricted TAAs that circumvent conventional tolerance mechanisms. More recently, a key focus of interest is in immune presentation of post-translationally modified antigens, in particular phosphorylated peptides, which may provide an immunological signature of “transformed self” on tumours. Our phosophopeptide immunology research involves interactions with Dr Mark Cobbold, and various international collaborators. Collectively these studies will help us understand and exploit key clinically relevant immunotherapeutic targets and approaches.


Immunosurveillance and tumour targeting by unconventional T-cells

Compelling evidence also suggests unconventional lymphocytes including gamma delta T-cells play important roles in innate immunity to cancer by sensing and reacting to cellular stress. In mice, gamma delta T-cells mediate immune protection from cutaneous malignancy. In humans, numerous studies highlight killing of cancer cells by human gamma delta T-cells, and expansions in this T-cell subset correlate with lower rates of post-transplant malignancies. In addition, several clinical trials designed to elicit gamma delta T-cell anti-tumour immunity have achieved objective clinical responses in patients with either haematological (eg multiple myeloma) or solid (eg metastatic prostate cancer) maligancies. Moreover, a common and effective treatment for bladder cancer is vaccination with BCG, a mycobacterium known to stimulate both gamma delta and CD1-restricted T-cells. These findings strongly suggest the natural capacity of unconventional lymphocytes such as gamma delta T-cells to provide immunosurveillance and targeting of transformed cells may be effectively exploited in the clinic.

Our research is primarily focussed on characterising the molecular basis of gamma delta T-cell recognition. Despite overwhelming evidence for gamma delta T-cell recognition of tumours, the ligands recognised directly by gamma delta TCRs on tumour cells have remained largely unidentified. With national and international collaborators, we are identifying novel gamma delta TCR ligands and using molecular and structural techniques to characterise key receptor ligand interactions. A second area has focussed on understanding CD1-restricted responses to mycobacterial lipid antigens. Collectively, these studies will shed new light on immune recognition by unconventional lymphocytes, and in doing so facilitate design of improved cancer immunotherapy approaches.


Therapeutic application of immune receptors in cancer immunotherapy

A final aim is to extend our basic immunology studies in order to apply our molecular insights to improved targeting strategies for cancer treatment. In this area, we have several ongoing collaborations both within the CRUK Centre and with other UK or international groups to understand and explore both targeting of novel TAAs, and tumour targeting by unconventional lymphocytes.

Other activities

Outreach charity work for Cancer Research UK, including at local fundraising events, local media events, and laboratory tours.

Publications

Recent publications

Article

Faustini, S, Jossi, S, Perez-Toledo, M, Shields, A, Allen, JD, Watanabe, Y, Newby, ML, Cook, A, Willcox, C, Salim, M, Goodall, M, Heaney, J, Marcial-Juarez, E, Morley, G, Torlinska, B, Wraith, D, Veenith, T, Harding, S, Jolles, S, Mark, PJ, Plant, T, Huissoon, A, O’Shea, MK, Willcox, B, Drayson, M, Crispin, M, Cunningham, A & Richter, A 2021, 'Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva', Immunology. https://doi.org/10.1111/imm.13349

Karunakaran, MM, Willcox, CR, Salim, M, Paletta, D, Fichtner, AS, Noll, A, Starick, L, Nöhren, A, Begley, CR, Berwick, KA, Chaleil, RAG, Pitard, V, Déchanet-merville, J, Bates, PA, Kimmel, B, Knowles, TJ, Kunzmann, V, Walter, L, Jeeves, M, Mohammed, F, Willcox, BE & Herrmann, T 2020, 'Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing', Immunity, vol. 52, no. 3, pp. 487-498.e6. https://doi.org/10.1016/j.immuni.2020.02.014

Faustini, SE, Jossi, SE, Perez-Toledo, M, Shields, A, Allen, JD, Watanabe, Y, Newby, ML, Cook, A, Willcox, CR, Salim, M, Goodall, M, Heaney, JL, Marcial-Juarez, E, Morley, GL, Torlinska, B, Wraith, DC, Veenith, T, Harding, S, Jolles, S, Mark, PJ, Plant, T, Huissoon, A, O'Shea, MK, Willcox, BE, Drayson, MT, Crispin, M, Cunningham, AF & Richter, AG 2020, 'Detection of antibodies to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances detection of infection', medRxiv. https://doi.org/10.1101/2020.06.16.20133025

Willcox, CR, Mohammed, F & Willcox, BE 2020, 'The distinct MHC‐unrestricted immunobiology of innate‐like and adaptive‐like human γδ T cell subsets—Nature's CAR‐T cells', Immunological Reviews, vol. 298, no. 1, pp. 25-46. https://doi.org/10.1111/imr.12928

Willcox, BE, Mohammed, F & Willcox, CR 2020, 'γδ TCR Recognition of MR1: Adapting to Life on the Flip Side', Trends in Biochemical Sciences, vol. 45, no. 7, pp. 551-553. https://doi.org/10.1016/j.tibs.2020.03.012

Willcox, C, Vantourout, P, Salim, M, Zlatareva, I, Melandri, D, Zanardo, L, George, R, Kjaer, S, Jeeves, M, Mohammed, F, Hayday, AC & Willcox, B 2019, 'Butyrophilin-like 3 directly binds a human Vγ4+ t cell receptor using a modality distinct from clonally-restricted antigen', Immunity, vol. 51, no. 5, pp. 813-825.e4. https://doi.org/10.1016/j.immuni.2019.09.006

Brooks, J, Antao Mobre De Menezes, ARE, Ibrahim, M, Archer, L, Lal, N, Bagnall, C, Zeidler, SVV, Valentine, H, Spruce, R, Batis, N, Bryant, J, Hartley, M, Kaul, B, Ryan, G, Bao, R, Khattri, A, Lee, S, Ogbureke, KUE, Middleton, G, Tennant, D, Beggs, A, Deeks, J, West, CML, Cazier, J-B, Willcox, B, Seiwert, TY & Mehanna, H 2019, 'Development and validation of a combined hypoxia and immune prognostic classifier for head and neck cancer', Clinical Cancer Research, vol. 25, no. 17, pp. 5315-5328. https://doi.org/10.1158/1078-0432.CCR-18-3314

Thomas, S, Mohammed, F, Reijmers, R, Woolston, A, Stauss, T, Kennedy, A, Stirling, D, Holler, A, Green, L, Jones, D, Matthews, KK, Price, DA, Chain, B, Heemskerk, MHM, Morris, E, Willcox, B & Stauss, HJ 2019, 'Framework engineering to produce dominant T cell receptors with enhanced antigen-specific function', Nature Communications, vol. 10, no. 1, 4451. https://doi.org/10.1038/s41467-019-12441-w

Mohammed, F, Stones, D & Willcox, B 2018, 'Application of the immunoregulatory receptor LILRB1 as a crystallisation chaperone for human class I MHC complexes', Journal of Immunological Methods. https://doi.org/10.1016/j.jim.2018.10.011

Hunter, S, Willcox, C, Davey, M, Kasatskaya, SA, Jeffery, H, Chudakov, D, Oo, Y & Willcox, B 2018, 'Human liver infiltrating γδ T cells are composed of clonally expanded circulating and tissue-resident populations', Journal of Hepatology, vol. 69, no. 3, pp. 654-665. https://doi.org/10.1016/j.jhep.2018.05.007

Davey, MS, Malde, R, Mykura, RC, Baker, AT, Taher, TE, Le Duff, CS, Willcox, BE & Mehellou, Y 2018, 'Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-Methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cells Immune Response', Journal of Medicinal Chemistry, vol. 61, no. 5, pp. 2111-2117. https://doi.org/10.1021/acs.jmedchem.7b01824

Davey, M, Willcox, C, Hunter, S, Kasatskaya, SA, Remmerswaal, EBM, Salim, M, Mohammed, F, Bemelman, FJ, Chudakov, DM, Oo, YH & Willcox, B 2018, 'The human Vδ2+ T-cell compartment comprises distinct innate-like Vγ9+ and adaptive Vγ9- subsets', Nature Communications, vol. 9, no. 1, 1760. https://doi.org/10.1038/s41467-018-04076-0

Abstract

Mehanna, HM, Brooks, J, Menezes, A, Ibrahim, M, Lal, N, Archer, L, Zeidler, SV, Bao, R, Khattri, A, Valentine, H, Spruce, R, Batis, N, Bryant, J, Beggs, AD, Tennant, D, West, C, Middleton, GW, Cazier, J-B, Willcox, B & Seiwert, TY 2018, 'Development and validation of a combined metabolic and immune prognostic classifier for head and neck cancer', Journal of Clinical Oncology, vol. 36, no. 15 Suppl, pp. 6049-6049. https://doi.org/10.1200/jco.2018.36.15_suppl.6049

Review article

Willcox, C, Davey, M & Willcox, B 2018, 'Development and selection of the human Vγ9Vδ2+ T- cell repertoire', Frontiers in immunology, vol. 9, 1501. https://doi.org/10.3389/fimmu.2018.01501

Davey, M, Willcox, C, Baker, A, Hunter, S & Willcox, B 2018, 'Recasting Human Vδ1 Lymphocytes in an Adaptive Role', Trends in Immunology, vol. 39, no. 6, pp. 446-459. https://doi.org/10.1016/j.it.2018.03.003

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