Professor Benjamin Willcox BA, DPhil

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

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.

• Intercalated BmedSc in Clinical Sciences
  Lecture on “Protein 3D structure determination by X-ray crystallography”
• MSc in Clinical Oncology
  Lecture in Module 1 on “Introduction to Cellular Immunology”
• MBChB 2nd year course “Cancer Causes to Cures”
• Small group teaching on “Primary and Secondary Cancer Prevention”
• Lead organiser, MRes Laboratory Practical Week 4: Experimental approaches; Structural Biology component (2011-) Lecture: “Protein analysis and biophysics”
• Lead organiser, 2011-2012 MRes Cancer Module

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 Ben on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

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.

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