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Medicine

Professor Stephen Beers 

Professor of Immunology and Immunotherapy

Professor Stephen Beers's photo

Professor Stephen Beers is Professor of Immunology and Immunotherapy at the Centre for Cancer Immunology in the Faculty of Medicine at the University of Southampton.

Antibody immunotherapy is transforming how cancer patients are treated. Despite the success of antibody drugs not all patients respond and few are cured. Our aim is to understand the role of macrophages in cancer and generate immune strategies to harness their full potential to kill malignant cells and cure patients.

Stephen Beers graduated from the University of Southampton in 1999 with a first class degree in Biochemistry. Subsequently he was awarded a personal PhD studentship from the BBSRC and graduated in 2003. He then moved to the Cancer Sciences Division (CSD) in the Faculty of Medicine and undertook his first postdoctoral fellowship in Immunochemistry and Immunotherapy. Following two successful postdoctoral positions he was awarded a career track fellowship and established his own group studying antibody effector function.

His research group is interested in how antibodies work to result in tumour regression. The research is currently focused on how the tumour microenvironment, particularly macrophages, affect effector function and how this could be manipulated to enhance antibody efficacy in patients. They have built a portfolio of complimentary models incorporating in vitro 3D modelling, appropriate in vivo model systems and primary clinical material.

The research group currently comprises; Dr Charles Birts, Against Breast Cancer Lecturer in Antibody Therapeutics (a joint appointment with Professor Max Crispin, Biological Sciences), two postdoctoral fellows, two research technicians, four PhD students, and two clinical fellows.

Qualifications

BSc (Hons), Biochemistry 1st Class, University of Southampton, 1999
PhD, Biochemistry, University of Southampton, 2003

Research interests

Antibody Effector Functions

Monoclonal antibodies (mAb) have become established in the treatment of a variety of malignancies - transforming patient outcomes. Despite this undoubted impact, responses remain variable and their mechanisms of action and of tumour resistance are controversial. Our research is focussed on understanding these complex processes using a variety of complementary models and systems to better inform antibody selection, design and clinical application.

Current research interests:

  1. Manipulating tumour microenvironment and effector function to enhance antibody therapy
    Antibody immunotherapy relies predominantly on activatory Fc-gamma-Receptors (FcγR) expressing macrophages for effector function. However, tumour associated macrophages have a pro-tumour, anti-inflammatory phenotype associated with a poor prognosis and response to a variety of therapeutic interventions. The understanding of how macrophages are manipulated by tumours in vivo and how they may be re-programmed to augment mAb immunotherapy is a critical area of study where data is currently lacking.
  2. How antibodies that directly target tumours induce therapeutic responses and may be augmented by other reagents
    This area of research concerns a continuing interest, how monoclonal antibodies (mAb) achieve their therapeutic success. This concerns a variety of tumour targets and in particular the anti-CD20 mAb rituximab which is one of only a handful of mAb that have proven efficacious in the clinic. Our focus has been to delineate the key effector mechanisms employed by anti-CD20 mAb in vivo. Antibody mediated immunotherapy is purported to have three main mechanisms available for activity; complement dependent cytotoxicity, induction of programmed cell death and Fc:FcγR effector functions but we have recently demonstrated that only the latter is required for the depletion of normal B cells in vivo. We have found that some mAb lead to the internalisation of CD20 from the B cell surface and that this modulation has two concomitant effects; firstly it reduces effector cell mediated cell clearance and reduces the half-life of the antibodies in vivo. We have extended this work to encompass a range of lymphomas and found a correlation between internalisation and disease susceptibility to Rituximab therapy such that CD20 was rapidly internalised from the surface of most primary CLL (chronic lymphocytic leukaemia) and MCL (mantle cell lymphoma) cells, thus limiting engagement of anti-tumour effector mechanisms. Far less internalisation was observed in the majority of FL (follicular lymphoma) and DLBCL (diffuse large B cell lymphoma) samples, which may relate to their better clinical responses to rituximab.
  3. The requirement for Fc receptors and effector cell interactions for immunomodulatory mAb
    These antibodies represent a new and exciting branch of immunotherapy where the target cells for the therapy are not the tumour itself but effector cells of the innate and adaptive immune system. These mAb are able in this way to harness and redirect the powerful capabilities of the patient’s immune system to fight the cancer itself. We have found that the mAb isotype best able to elicit strong immunostimulatory signals and therapy differ markedly from that required for conventional targeted mAb therapy as typified by rituximab. Using a variety of models unique to Southampton we are currently dissecting the mechanisms and cells required for their activity and therapeutic efficacy.

Funding: Against Breast Cancer, Cancer Research UK, Willberry’s Research

Centre for Cancer Immunology, Cancer Sciences

Research group

Cancer Sciences

Postgraduate student supervision

Thomas Tipton (2015) PhD, Lang Dou (2016) PhD, Michael Marshall (2018) PhD, Emily Webb (2018) PhD

National and International Responsibilities

Main organiser for Federation of American Societies For Experimental Biology Scientific Research Conference ‘Immunoreceptors and Immunotherapy’ 2020

Scientific Review Panel Member for FRIMEDBIO, Research Council of Norway

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BM5 Immunology subject lead, lecturer and tutor on Year 1 and 2 Immunology Courses.

BMedSc/MMedSc Provides laboratory based projects and research journal club tutorials. Offers 1-2 project placements that investigate direct targeting and immunomodulatory antibody therapy, tumour microenvironment and effector function.

Integrated PhD Cancer Pathway Lecturer and tutor for ‘Host Immunity to Cancer’ and provides laboratory based research projects. Offers 1-2 project placements that investigate direct targeting and immunomodulatory antibody therapy, tumour microenvironment and effector function.

Professor Stephen Beers
Antibody and Vaccine Group
Centre for Cancer Immunology
Faculty of Medicine
University of Southampton
Southampton General Hospital
Mailpoint 127
Tremona Road
Southampton
SO16 6YD

Room Number: SGH/CCI/MP127

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