Beers, Stephen - University of Southampton

个人简介

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 within the School of Medicine. He has now established his own research group within Cancer Sciences 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 affects effector function and how this could be manipulated to enhance antibody efficacy in patients. They are currently building a portfolio of complimentary models incorporating in vitro 3D modelling, appropriate in vivo model systems and primary clinical material. The research group currently comprises five postdoctoral fellows, one research technician, two PhD students, and two undergraduate students.

研究领域

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: Manipulating tumour microenvironment and effector function to enhance antibody therapy. How Type I and II anti-CD20 antibodies induce therapeutic responses and may be augmented by other reagents. The requirement for Fc receptors and effector cell interactions for immunomodulatory mAb. 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. How Type I and II anti-CD20 antibodies 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 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. The requirement for Fc receptors and effector cell interactions for immunomodulatory mAb These mAb 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.

近期论文

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Antitumor efficacy of radiation plus immunotherapy depends upon dendritic cell activation of effector CD8+ T cells - Dovedi, Simon, Lipowska-Bhalla, Grazyna, Beers, Stephen A., Cheadle, Eleanor J., Mu, Lijun, Glennie, Martin J., Illidge, Timothy M. and Honeychurch, Jamie Published:2016Publication:Cancer Immunology ResearchVolume:7, (4)Page Range:621-630doi:10.1158/2326-6066.CIR-15-0253PMID:27241845 A combination of trastuzumab and BAG-1 inhibition synergistically targets HER2 positive breast cancer cells - Papadakis, E.S., Robson, N.H., Yeomans, A., Bailey, S., Laversin, S., Beers, S., Sayan, A., Ashton-Key, M., Schwaiger, S., Stuppner, H., Troppmair, J., Packham, Graham and Cutress, Ramsey Published:2016Publication:OncotargetPage Range:1-14doi:10.18632/oncotarget.7944PMID:26958811 Influence of immunoglobulin isotype on therapeutic antibody function - Beers, S., Glennie, M. and White, A. Published:2016Publication:BloodVolume:127, (9)Page Range:1-6doi:10.1182/blood-2015-09-625343PMID:26764357 Anti-mouse Fc?RIV antibody 9E9 also blocks Fc?RIII in vivo - Tipton, T., Mockridge, C., French, R., Tutt, A., Cragg, M. and Beers, S. Published:2015Publication:BloodVolume:126, (24)Page Range:2643-2645doi:doi: 10.1182/blood-2015-09-671339PMID:26492935