Professor Benjamin Willcox BA, DPhil

Benjamin Willcox

Institute of Immunology and Immunotherapy
Head of Department of Immunology and Immunotherapy
Professor of Molecular Immunology

Contact details

Address
Department of Immunology and Immunotherapy

Ben Willcox is based in the Department of Immunology and Immunotherapy as Professor of Molecular Immunology and was the Cancer Research UK Birmingham Centre Scientific Director between 2017-2022.

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 Medicine and Health's 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.

Ben is Head of Department of Department of Immunology and Immunotherapy.

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

Syrimi, E, Khan, N, Murray, P, Willcox, C, Haigh, T, Willcox, B, Masand, N, Bowen, C, Dimakou, DB, Zuo, J, Barone, SM, Irish, JM, Kearns, P & Taylor, GS 2024, 'Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling', iScience. https://doi.org/10.1016/j.isci.2024.110837

Brooks, JM, Zheng, Y, Hunter, K, Willcox, BE, Dunn, J, Nankivell, P, Gevaert, O & Mehanna, H 2024, 'Digital Spatial Profiling identifies distinct patterns of immuno-oncology-related gene expression within oropharyngeal tumours in relation to HPV and p16 status', Frontiers in Oncology, vol. 14, 1428741. https://doi.org/10.3389/fonc.2024.1428741

Xu, Q, Sharif, M, James, E, Dismorr, JO, Tucker, JHR, Willcox, BE & Mehellou, Y 2024, 'Phosphonodiamidate prodrugs of phosphoantigens (ProPAgens) exhibit potent Vγ9/Vδ2 T cell activation and eradication of cancer cells', RSC Medicinal Chemistry, vol. 15, no. 7, pp. 2462-2473. https://doi.org/10.1039/d4md00208c

Karunakaran, MM, Subramanian, H, Jin, Y, Mohammed, F, Kimmel, B, Juraske, C, Starick, L, Nöhren, A, Länder, N, Willcox, CR, Singh, R, Schamel, WW, Nikolaev, VO, Kunzmann, V, Wiemer, AJ, Willcox, BE & Herrmann, T 2023, 'A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing', Nature Communications, vol. 14, no. 1, 7617 . https://doi.org/10.1038/s41467-023-41938-8

Talhouni, S, Fadhil, W, Mongan, NP, Field, L, Hunter, K, Makhsous, S, Maciel-Guerra, A, Kaur, N, Nestarenkaite, A, Laurinavicius, A, Willcox, BE, Dottorini, T, Spendlove, I, Jackson, AM, Ilyas, M & Ramage, JM 2023, 'Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers', Frontiers in immunology, vol. 14, 3389. https://doi.org/10.3389/fimmu.2023.1057292

Degirmencay, A, Thomas, S, Mohammed, F, Willcox, BE & Stauss, HJ 2023, 'Modifications outside CDR1, 2 and 3 of the TCR variable β domain increase TCR expression and antigen-specific function', Frontiers in immunology, vol. 14, 1148890. https://doi.org/10.3389/fimmu.2023.1148890

Willcox, CR, Salim, M, Begley, CR, Karunakaran, MM, Easton, EJ, von Klopotek, C, Berwick, KA, Herrmann, T, Mohammed, F, Jeeves, M & Willcox, BE 2023, 'Phosphoantigen sensing combines TCR-dependent recognition of the BTN3A IgV domain and germline interaction with BTN2A1', Cell Reports, vol. 42, no. 4, 112321. https://doi.org/10.1016/j.celrep.2023.112321

McMurray, J, von Borstel, A, Taher, T, Syrimi, E, Taylor, G, Sharif, M, Rossjohn, J, Remmerswaal, E, Bemelman, F, Vieira Braga, FA, Chen, X, Teichmann, SA, Mohammed, F, Berry, A, Lyke, K, Williamson, K, Stubbington, M, Davey, M, Willcox, C & Willcox, B 2022, 'Transcriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program', Cell Reports, vol. 39, no. 8, 110858. https://doi.org/10.1016/j.celrep.2022.110858

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, vol. 164, no. 1, pp. 135-147. https://doi.org/10.1111/imm.13349

Kadri, H, Taher, TE, Xu, Q, Sharif, M, Ashby, E, Bryan, RT, Willcox, BE & Mehellou, Y 2020, 'Aryloxy Diester Phosphonamidate Prodrugs of Phosphoantigens (ProPAgens) as Potent Activators of Vγ9/Vδ2 T-Cell Immune Responses', Journal of Medicinal Chemistry, vol. 63, no. 19, pp. 11258-11270. https://doi.org/10.1021/acs.jmedchem.0c01232

Kadri, H, Taher, T, Xu, Q, Sharif, M, Ashby, E, Bryan, R, Willcox, B & Mehellou, Y 2020, 'Aryloxy diester phosphonamidate prodrugs of phosphoantigens (ProPAgens) as potent activators of Vγ9/Vδ2 T‐cell immune responses', Journal of Medicinal Chemistry, vol. 63, no. 19, pp. 11258-11270.

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

Letter

Perez-Toledo, M, Faustini, SE, Jossi, SE, Shields, AM, Marcial‐Juarez, E, Kanthimathinathan, HK, Allen, JD, Watanabe, Y, Goodall, M, Willcox, BE, Willcox, CR, Salim, M, Wraith, DC, Veenith, TV, Syrimi, E, Drayson, MT, Jyothish, D, Al‐Abadi, E, Chikermane, A, Welch, SB, Masilamani, K, Hackett, S, Crispin, M, Scholefield, BR, Cunningham, AF & Richter, AG 2021, 'SARS‐CoV‐2‐specific IgG1/IgG3 but not IgM in children with Pediatric Inflammatory Multi‐System Syndrome', Pediatric allergy and immunology, vol. 32, no. 5, pp. 1125-1129. https://doi.org/10.1111/pai.13504

Preprint

Pugh, M, Fennell, E, Leahy, CI, Perry, T, Hargitai, B, Marton, T, Hunter, K, Halford, G, Yilmaz, HO, Stamataki, Z, Reynolds, G, Hill, HJ, Willcox, BE, Steven, N, Thornton, CA, Dojcinov, SD, Culhane, A, Murray, PG & Taylor, GS 2022 'Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis' bioRxiv. https://doi.org/10.1101/2022.11.14.516398

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