Dr Mark Cobbold is working on understanding how the human immune response detects and eliminates cancer. His group identifies which tumour antigens human immune cells target and is developing new immune based therapies to replace failed anti-cancer immunity in patients with cancer.
Senior Clinical Research Fellow, School of Immunity and Infection, University of Birmingham.
Background and Research focus
Mark Cobbold is currently a Senior Clinical Research Fellow based at the medical school in University of Birmingham. He qualified in medicine in 1995 from the University of Edinburgh, and then began his scientific career in Birmingham in 2000 where, under Paul Moss, he studied cellular immunotherapy for patients who had received stem cell transplants (SCT), receiving a PhD in 2005. During this period he pioneered a novel T cell selection technology for manipulating and selecting antigen-specific cells for therapeutic use, and conducted a successful Phase I clinical trial using cytomegalovirus (CMV) specific T-cells.
This early work led him to become interested in how donor immunity is able to cure a recipient of cancer, and he was successful in obtaining an MRC Clinician Scientist Fellowship to advance this work whilst undertaking clinical training in Clinical Immunology. As part of this fellowship he spent 2-years at the University of Virginia with Don Hunt and Vic Engelhard and became interested in novel tumour antigens. This work identified over 100 novel phosphorylated tumour antigens on primary leukaemia samples. He has demonstrated the clinical relevance of these antigens and shown that immune responses against a subset of these may contribute toward graft versus leukaemia effect of SCT. Subsequent studies have focused on colorectal, pancreatic and oesophageal adenocarcinoma tumours.
On returning to the UK he set up a research laboratory that focuses on tumour immunology. A key theme of his research group is translationally oriented projects which aim to bridge the gap between basic research and patient care. In addition to identifying novel tumour-associated post-translationally modified antigens his lab has defined a new method by which tumour cells can process exogenously presented antigens. By modulating the tumour antigen display, the technology effectively mimics a viral infection within the tumour and allows highly cytotoxic virus-specific T-cells to specifically control the tumour.
Tumour antigen identification; therapeutic antibody engineering; cell separation; tumour immunology; phosphopeptide immunology; antigen presentation; adoptive transfer; immunotherapy.
In addition to running his research group, Mark spends approximately 10% in the NHS, his medical specialty being clinical immunology, and is closely involved in running the Birmingham Clinical Immunology Service. He is a founding member of a team that developed a novel cancer diagnostic for the diagnosis and management of myeloma and formed a spin-out company, SeraScience Ltd, in 2012. Mark is also a co-founder of PhosImmune Inc, a company developing cancer vaccines targeting phosphopeptide antigens.
Campbell JP, Cobbold M, Wang Y, Goodall M, Bonney SL, Chamba A, Birtwistle J, Plant T, Afzal Z, Jefferis R, Drayson MT. Development of a highly-sensitive multi-plex assay using monoclonal antibodies for the simultaneous measurement of kappa and lambda immunoglobulin free light chains in serum and urine. J Immunol Methods. 2013 May 31;391(1-2):1-13.
Chakupurakal G, Onion D, Bonney S, Cobbold M, Mautner V, Moss P. HLA-peptide multimer selection of adenovirus-specific T cells for adoptive T-cell therapy. J Immunother. 2013 Oct;36(8):423-31.
Cobbold M, De La Pena H, Norris A, Polefrone JM, Qian J, English AM, Cummings KL, Penny S, Turner JE, Cottine J, Abelin JG, Malaker SA, Zarling AL, Huang HW, Goodyear O, Freeman SD, Shabanowitz J, Pratt G, Craddock C, Williams ME, Hunt DF, Engelhard VH. MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. Sci Transl Med. 2013 Sep 18;5(203):203ra125.
Nicholls S, Piper KP, Mohammed F, Dafforn TR, Tenzer S, Salim M, Mahendra P, Craddock C, van Endert P, Schild H, Cobbold M, Engelhard VH, Moss PA, Willcox BE. Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3889-94.
Mohammed F, Cobbold M, Zarling AL, Salim M, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Engelhard VH, Willcox BE. Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self. Nat Immunol. 2008 Nov;9(11):1236-43.
Cobbold M, Khan N, Pourgheysari B, Tauro S, McDonald D, Osman H, Assenmacher M, Billingham L, Steward C, Crawley C, Olavarria E, Goldman J, Chakraverty R, Mahendra P, Craddock C, Moss PA. Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med. 2005 Aug 1;202(3):379-86. PubMed PMID: 16061727; PubMed Central PMCID: PMC2213070.
Moss PA, Cobbold M, Craddock C. The cellular immunotherapy of viral infection. Transfus Med. 2003 Dec;13(6):405-15. Review. PubMed PMID: 14651746.