Tumour Immunology, Cellular and Gene Therapy

Academic Team Leaders
Professor Hans Stauss,
Dr Emma Morris and
Dr Shao-An Xue

Summary

The main focus of our work is the analysis of antigen-specific T lymphocyte responses to tumours and the development of immunotherapy approaches for cancer treatment. The transfer of T cell receptor (TCR) genes provides an exciting strategy to equip patient T lymphocytes with well-characterized TCRs, allowing the gene modified T cells to attack tumour cells. We also use the TCR transfer approach to explore whether it can control EBV associated malignancies and CMV spread in immunosuppressed individuals. Our experimental platform involves extensive in vitro analysis of target antigen expression and the definition of effective T cell responses. We use in vivo murine models to test safety and efficacy of new immunotherapy protocols, and are currently translating our research into phase I/II clinical trials with the goal of establishing effective immunity in patients.

Active Research Projects

Currently, the following translational and basic research projects are performed in the Tumour Immunology Research Group:

• A clinical phase I/II peptide vaccination trial in leukaemia patients

• Construction and validation of retroviral vectors suitable for clinical TCR gene therapy trials in patients with leukaemia and solid tumours

• A clinical phase I/II TCR gene therapy trial in Leukaemia patients (to open mid 2008)

• Construction and validation of lentiviral vectors for TCR gene transfer

• Analysis of local and systemic T cell responses against tumour-associated antigens in patients with leukaemia and solid tumours

• In vivo analysis of TCR gene modified T cells in murine models: mechanisms of CD4 and CD8 T cell interaction, T cell migration, survival and memory development.

• Production of modified TCRs to prevent pairing with endogenous TCRs

• Mapping TCR domains dictating T cell effector function

• Assessing the functional activity of TCRs that were affinity matured in vitro by phage display

• Analysis of tolerance mechanisms in a TCR transgenic murine model

• Use of dendritic cell vaccination strategies in murine models

• CD8 co-receptor modification to improve T cell functional avidity against tumour associated antigens

You can find out further information about the group’s research at UCL’s Cancer Institute website (http://www.ucl.ac.uk/cancer/research-groups/tumour-immunology/index.htm).  Other sources of information about the Division's research are available in the School of Life & Medical Sciences People Pages and UCL's Research Publications Database

Research Group Members
(UCL IRIS Research Profiles are linked where available)

Professor Hans Stauss MD PhD
Email: h.stauss@_ucl.ac.uk
UCLP Immunology & Transplantation , IRIS

Dr Emma Morris PhD, MRCP, MRCPath, Reader
Email: e.morris@_ucl.ac.uk
IRIS

Dr Shao-An Xue PhD, Senior Lecturer
Email: shao-an.xue@_ucl.ac.uk
IRIS

Dr Liquan Gao MD, Senior Research Fellow
Email: liquan.gao@_ucl.ac.uk
IRIS

Mrs Eira Rawlings MSc HND, Laboratory Manager
Email: e.rawlings@_ucl.ac.uk

Dr Maryam Ahmadi PhD, Postdoctoral Scientist
Email: Maryam.ahmadi@_ucl.ac.uk
IRIS

Ms Lyn Ambrose MSc, Research Technician
Email: l.ambrose@_ucl.ac.uk

Dr Ben Carpenter MBBS, Clinical Research Fellow/PhD Student
Email: benjamin.carpenter@_ucl.ac.uk

Dr Ignatius Chua MB BS, Clinical Research Fellow/PhD Student
Email: i.chua@_ucl.ac.uk

Dr Sara Ghorashian MBBS, Clinical Research Fellow/PhD Student Email: s.ghorashian@_ucl.ac.uk

Mr David Guzman Lic, Database Manager/Developer
Email: d.guzman@_ucl.ac.uk

Ms Angelika Holler MSc, Research Technician
Email: a.holler@_ucl.ac.uk

Dr Irma Martinez-Davila PhD, Postdoctoral Scientist
Email: i.martinez-davila@_ucl.ac.uk

Dr Emma Nicholson MBBS, Clinical Research Fellow/PhD Student
Email: e.nicholson@_ucl.ac.uk

Dr Rebecca Pike PhD, Research Technician
Email: r.pike@_ucl.ac.uk

Dr Maria Serrano PhD, Clinical Trial Coordinator
Email: m.serrano@_ucl.ac.uk

Ms Maria Stavrou, MSc, UCL Grand Challenges PhD Student
Email: maria.stavrou.10@_ucl.ac.uk

Dr Sharyn Thomas PhD, Postdoctoral Scientist
Email: s.thomas@_ucl.ac.uk
IRIS

Dr Ben Uttenthal MBBS, Clinical Research Fellow/PhD Student
Email: benjamin.uttenthal@_ucl.ac.uk

Mrs Jennifer Wanders MSc, Research Technician
Email: j.wanders@_ucl.ac.uk

Current Funding Sources: Leukaemia Research; Medical Research Council; Cancer Research UK; European Union; Dinwoodie Trust; and the UK Department of Health.

Recent Selected Publications

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

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

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

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

Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis. Wright GP, Notley CA, Xue SA, Bendle GM, Holler A, Schumacher TN, Ehrenstein MR, Stauss HJ.
Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19078-83.

Development of a Wilms' tumor antigen-specific T-cell receptor for clinical trials: engineered patient's T cells can eliminate autologous leukemia blasts in NOD/SCID mice.
Xue SA, Gao L, Thomas S, Hart DP, Xue JZ, Gillmore R, Voss RH, Morris E, Stauss HJ.
Haematologica. 2010 Jan;95(1):126-34.

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