Prof Hans Stauss

Research projects
Hans Stauss

Prof Hans Stauss

Director Institute of Immunity and Transplantation

Co-director Division of Infection and Immunity

Prof. Hans Stauss

Contact

Professor Hans J Stauss
Institute of Immunity and Transplantation
University College London
Royal Free Hospital
Rowland Hill Street
London NW3 2PF 
UK
h.stauss [at] ucl.ac.uk
T. +44 (0)20 7794 0500  Ext. 33321

Research area

Cancer Immunology

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 Dr 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.

Group members

Ahdab Alsaieedi
David Guzman
Angelika Holler
Alistair Hotblack
Rebecca Pike
Francis Robertson
Maria Stavrou
Sharyn Thomas
Niclas Thomas
Graham Wright
Shao-An Xue

Recent publications

Cellerai C, Harari A, Stauss H, Yerly S, Geretti AM, Carroll A, Yee T, Ainsworth J, Williams I, Sweeney J, Freedman A, Johnson M, Pantaleo G, Kinloch-de Loes S.Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.  PLoS One. 2011 Apr 5;6(4):e18164

Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss HJ, Bertoletti A. Engineering Virus-specific T cells that Target HBV Infected Hepatocytes and Hepatocellular Carcinoma Cell Lines.  J Hepatol. 2011 Jul;55(1):103-10

Pospori, C SA Xue, SA.,  A Holler, A., C Voisine, C., Perro, M., King, J., Fallah-Arani, F., Flutter, B., R Chakraverty, R., Stauss, HJ* and Morris, EC* (*joint senior authors). Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination. Blood, 2011 Jun 23;117(25):6813-24

Thomas S, Xue SA, Bangham C, Jakobsen BK, Morris E, Stauss HJ.  Human T cells expressing affinity matured TCR display accelerated responses but fail to recognise low density of MHC/peptide antigen. Blood. 2011,  Jul 14;118(2):319-29

Ahmadi, M., King, JW., Xue, SA., Voisine, C., Holler, A., Wright, GP., Waxman, J., Morris, EC., Stauss, HJ. CD3 limits the Efficacy of TCR Gene Therapy in vivo. Blood. 2011, Sep 29;118(13):3528-37

Simpson AA, Mohammed F, Salim M, Tranter A, Rickinson AB, Stauss HJ, Moss PA, Steven NM, Willcox BE. Structural and energetic evidence for highly peptide-specific tumor antigen targeting via allo-MHC restriction. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21176-81

Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, Simon AK, Moutschen M, Etzioni A, Mory A, Srugo I, Melamed D, Hultenby K, Liu C, Baronio M, Vitali M, Philippet P, Dideberg V, Aghamohammadi A, Rezaei N, Enright V, Du L, Salzer U, Eibel H, Pfeifer D, Veelken H, Stauss HJ, Lougaris V, Plebani A, Gertz EM, Schäffer AA, Hammarström L, Grimbacher B. Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and Autoimmunity. Am J Hum Genet. 2012, 90(6):986-1001

Xue, SA, Gao, L, Ahmadi, M, Ghorashian, S, Pospori, C, Holler, A, Wright, G, Thomas, S, Topp, M, Morris, EC, Stauss, HJ. Human MHC class I-restricted CD4+ T cells specific for Epstein-Barr Virus and Cytomegalovirus provide protective immunity in vivo. Oncoimmunology. 2013 Jan 1;2(1):e22590

Field AC, Vink C, Gabriel R, Al-Subki R, Schmidt M, Goulden N, Stauss H, Thrasher A, Morris E, Qasim W. Comparison of lentiviral and sleeping beauty mediated αβ T cell receptor gene transfer. PLoS One. 2013 Jun 28;8(6):e68201

Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Wu Howland S, Ong AS, Gehring AJ, Stauss H, Renia L, Sällberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2:e114.

Snauwaert S, Verstichel G, Bonte S, Goetgeluk G, Vanhee S, Van Caeneghem Y, De Mulder K, Heirman C, Stauss H, Heemskerk MH, Taghon T, Leclercq G, Plum J, Langerak AW, Thielemans K, Kerre T, Vandekerckhove B.In vitro generation of mature, naive antigen-specific CD8+ T cells with a single T-cell receptor by agonist selection. Leukemia. 2013 Oct 4. 

Uttenthal B, Martinez-Davila I, Ivey A, Craddock C, Chen F, Virchis A, Kottaridis P, Grimwade D, Khwaja A, Stauss H, Morris EC. Wilms' Tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia induces short-lived WT1-specific immune responses. Br J Haematol. 2014 Feb;164(3):366-75. 

Sassi A, Lazaroski S, Wu G, Haslam SM, Fliegauf M, Mellouli F, Patiroglu T, Unal E, Ozdemir MA, Jouhadi Z, Khadir K, Ben-Khemis L, Ben-Ali M, Ben-Mustapha I, Borchani L, Pfeifer D, Jakob T, Khemiri M, Asplund AC, Gustafsson MO, Lundin KE, Falk-Sörqvist E, Moens LN, Gungor HE, Engelhardt KR, Dziadzio M, Stauss H, Fleckenstein B, Meier R, Prayitno K, Maul-Pavicic A, Schaffer S, Rakhmanov M, Henneke P, Kraus H, Eibel H, Kölsch U, Nadifi S, Nilsson M, Bejaoui M, Schäffer AA, Smith CI, Dell A, Barbouche MR, Grimbacher B. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immunol. 2014 May;133(5):1410-9

Qasim W, Brunetto M, Gehring A, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini M, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells targeting HBsAg in a liver transplant patient. J Hepatol. 2014 Oct 9. pii: S0168-8278

Older publications

Ramírez, F., Ghani, Y., Gao, L. and Stauss, H.J. Dendritic-cell immunization induces non-protective WT1-specific CTL responses in mouse. J. Immunother. (2007) 30:140-149.

Tamir A, Basagila E, Kagahzian A, Jiao L, Jensen S, Nicholls J, Tate P, Stamp G, Farzaneh F, Harrison P, Stauss HJ, George AJ, Habib N, Lechler RI, Lombardi G. Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother. 2007 Feb 23; [Epub ahead of print]

Bendle, G.M., Xue, S.A., Holler, A., Stauss, H.J. A Study of T Cell Tolerance to the Tumor-Associated Antigen MDM2: Cytokines Can Restore Antigen Responsiveness, but Not High Avidity T Cell Function, PLoS ONE. (2007) Apr 4;2:e353

McNicol, A.M., Bendle, G., Holler, A., Matjeka, T., Dalton, M., Rettig, R., Zamoyska, R., Uckert, W., Xue, S. and Stauss, H.J. CD8a/a homodimers fail to function as co-receptor for a CD8-dependent TCR. Eur J Immunol. (2007) Jun;37(6):1634-41. 

Nitcheu-Tefit, J., Dai, M., Critchley-Thorne, R.J., Ramirez, F., Xu, M., Conchon, S., Ferry, N., Stauss, H.J. and Vassaux, G. Listeriolysin-O expressed in a bacterial vaccine suppresses CD4+CD25high regulartory T cell function in vivo. J. Immunol. 2007 Aug 1; 179(3):1532-41.

Thomas, T., Xue, SA., Cesco-Gaspere, M., San José, E., Hart, DP., Wong, V., Debets, R., Alarcon, B., Morris, E., Stauss, HJ. Targeting the Wilms Tumor antigen 1 by TCR gene transfer: TCR variants improve tetramer binding but not the function of gene modified human T cells. J. Immunol. 2007; 179: 5803-5810.

Hart, DP., Xue, S., Sharyn Thomas, T., Cesco-Gaspere, M, Tranter, A., Willcox, B., Lee, SP., Steven, N., Morris, E. and Stauss, HJ. Retroviral transfer of a dominant TCR prevents surface expression of the endogenous TCR repertoire in human T cells. Gene Therapy 2008 Apr;15(8):625-31

Xue, S; Bendle, G., Holler, A. and Stauss, HJ. Generation and Characterisation of Transgenic mice expressing a T cell receptor specific for the tumor-associated antigen MDM2. Immunology 2008; 24(3):315-21

Leisegang M, Engels B, Meyerhuber P, Kieback E, Sommermeyer D, Xue SA, Reuß S, Stauss H, Uckert W. Enhanced functionality of T cell receptor-redirected T cells is defined by the transgene cassette. J Mol Med. 2008; 86(5):573-83.

Chaise C, Buchan SL, Rice J, Marquet J, Rouard H, Kuentz M, Vittes GE, Molinier-Frenkel V, Farcet JP, Stauss HJ, Delfau-Larue MH, Stevenson FK. DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance. Blood. 2008 Oct 1;112(7):2956-64

Tsang JY, Tanriver Y, Jiang S, Xue SA, Ratnasothy K, Chen D, Stauss HJ, Bucy RP, Lombardi G, Lechler R. Conferring indirect allospecificity on CD4CD25 Tregs by TCR gene transfer favors transplantation tolerance in mice. J Clin Invest. 2008 Nov 3;118(11):3619-3628

King, J., Thomas, S., Corsi, F., Gao, L., Dina, R., Gillmore, R., Pigott, K., Kaisary, A., Stauss,HJ. *  Waxman J.* IL15 can reverse the unresponsiveness of Wilms’ tumor antigen-specific CTL in patients with prostate cancer. Clin Cancer Res. 2009 Feb 15;15(4):1145-54. *Joint senior authors.

Wright, G.P., Clare A. Notley, C.A., Xue, S.A., Bendle, G.M., Holler, A., Schumacher, T.N., Michael R. Ehrenstein, M.R., Stauss, H.J. Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis. Proc. Natl. Acad. Sci. USA. 2009 Nov 10;106(45):19078-83

Dai MS, Nitcheu-Tefit J, Alcock S, Ramirez-Jimenez F, Chao TY, Baril P, Rocha M, Brett SJ, Stauss HJ, Vassaux G.; Development of an Escherichia coli Expressing Listeriolysin-O Vaccine Against Wilms Tumor Gene 1-expressing Tumors. J Immunother. 2009 Sep 11. [Epub ahead of print]

Xue, S., Gao, L., Thomas, S., Hart, D.P., Xue, J.Z., Gillmore, R., Voss, R.H., Morris, E. & Stauss, H.J. Development of a WT1-TCR for clinical trials: Engineered patient T cells can eliminate autologous leukemia blasts in NOD/SCID mice. Heamatologica; 2010 Jan;95(1):126-34

Perro, M., Tsang, J., Xue, SH., Escors, D., Cesco-Gaspere,M., Pospori,C., Gao,L., Hart, D., Collins, M., Stauss, HJ. and Morris, E. Generation of antigen-specific multi-functional human T cells by lentiviral TCR gene transfer. Gene Ther. 2010 Jun;17(6):721-32

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