Hans Stauss

Professor of Tumour Immunology
Director, Institute of Immunity & Transplantation

Research area

T cell immunology, with a particular focus on the role of the T cell receptor (TCR) in the recognition of cancer antigens.

Research programme

• Immunotherapy of cancer

Research summary

Cancer is a major health problem worldwide with WHO projections predicting an increase in incidence by 57% from 14 million cases in 2012 to 22 million cases by 2032. We are interested in exploring the role of the immune system in tumour development, and whether novel forms of immunotherapy can be used to treat cancer.

The research of our group is focussed on T cell immunology, with a particular focus the role of the T cell receptor (TCR) in the recognition of cancer antigens. We were amongst the first to show that cytotoxic T cells can selectively attack cancer cells by recognising point mutations in transforming proteins expressed in tumours (J Exp Med. 1993; 177:1493). We have since developed strategies to isolate monoclonal TCR that are specific for tumour antigens, and we use these TCR for gene therapy to redirected the specificity of patient T cells and equip them with the ability to selectively recognize and attack cancer cells.

The use of TCR gene therapy to produce antigen-specific cytotoxic and helper T cells is one area of active research in our group. We also use TCR and chimeric antigen receptor (CAR) gene transfer to produce antigen-specific regulatory T cells. This provides the opportunity to achieve highly selective immune suppression and treat autoimmune conditions without the need for systemic immune suppression.

We use gene transfer technologies to direct the functional profile of therapeutic T cells. We have developed genetic switches to enhance or suppress the metabolic activity of T cells, and this promote effector function or memory formation. Transfer of genes encoding transcription factors is used to drive Th1, Th2 or Th17 differentiation of adoptively transferred T cells. We perform studies with human T cells in vitro, and in immunodeficient mice in vivo. Murine models are used for mechanistic studies and to test therapeutic interventions in appropriate disease models.

Patient involvement

I work closely with my colleague Professor Emma Morris. We have active preclinical research programmes, and Emma is the chief investigator of clinical trials testing TCR gene therapy in patients. At present TCR gene therapy trials are open for patients with leukaemia and for patients who reactivate cytomegalovirus following haematopoietic stem cell transplantation. Additional TCR gene therapy trials are due to open soon.

Publications

Selected publications

• Thomas S, Mohammed F, Reijmers RM, Woolston A, Stauss T, Kennedy A, Stirling D, Holler A, Green L, Jones D, Matthews KK, Price DA, Chain BM, Heemskerk MHM, Morris EC, Willcox BE, Stauss HJ. Framework engineering to produce dominant T cell receptors with enhanced antigen-specific function. Nat Commun. 2019;10(1):4451.
• Zech MH, Velica P, Stauss HJ. T cell tuning for tumour therapy: Enhancing effector function and memory potential of therapeutic T cells. Curr Gene Ther. 2015;15(3):289-99
• Stauss HJ. Engineered T cells can fight malignant T cells. Blood. 2015;126(8):927-8
• Stauss HJ, Morris EC, Abken H. Cancer gene therapy with T cell receptors and chimeric antigen receptors. Curr Opin Pharmacol. 2015;24:113-8
• Holler A, Zech M, Ghorashian S, Pike R, Hotblack A, Veliça P, Xue SA, Chakraverty
• R, Morris EC, Stauss HJ. Expression of a dominant T-cell receptor can reduce toxicity and enhance tumor protection of allogeneic T-cell therapy. Haematologica. 2016;101(4):482-90
• Pike R, Thomas N, Workman S, Ambrose L, Guzman D, Sivakumaran S, Johnson M, Thorburn D, Harber M, Chain B, Stauss HJ. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients. Front Immunol. 2016;7:126
• Morris EC, Stauss HJ. Optimizing T-cell receptor gene therapy for hematologic malignancies. Blood. 2016;127(26):3305-11
• Geerdink JX, Simons SO, Pike R, Stauss HJ, Heijdra YF, Hurst JR. Differences in systemic adaptive immunity contribute to the 'frequent exacerbator' COPD phenotype. Respir Res. 2016;17(1):140
• Stauss HJ. Turn to TCRs when CARs fail. Oncotarget. 2017;8(8):12538-12539
• Stauss HJ. No hiding place for BOB inside myeloma. Blood. 2017;129(10):1236-1237
• McGovern JL, Wright GP, Stauss HJ. Engineering Specificity and Function of Therapeutic Regulatory T Cells. Front Immunol. 2017;8:1517
• Khan AB, Carpenter B, Santos E Sousa P, Pospori C, Khorshed R, Griffin J, Velica P, Zech M, Ghorashian S, Forrest C, Thomas S, Gonzalez Anton S, Ahmadi M, Holler A, Flutter B, Ramirez-Ortiz Z, Means TK, Bennett CL, Stauss H, Morris E, Lo Celso C, Chakraverty R. Redirection to the bone marrow improves T cell persistence and antitumor functions. J Clin Invest. 2018. pii: 97454
• Hotblack A, Holler A, Piapi A, Ward S, Stauss HJ, Bennett CL. Tumor-Resident Dendritic Cells and Macrophages Modulate the Accumulation of TCR-Engineered T Cells in Melanoma. Mol Ther. 2018. pii: S1525-0016(18)30119-9.

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