Awarded MBBS 2011
Awarded PhD 2012
T Cell Receptor Gene Transfer into Haematopoietic Stem Cells: a novel in vivo tumour immunotherapy model.
Dr Emma Morris, Dept of Immunology and Molecular Pathology, Royal Free Campus
Description of Project:
Clinical trials where the genes for a T cell receptor (TCR) with anti-tumour specificity are introduced into mature patient T cells and are then transferred back into the patient, are currently ongoing. These gene modified lymphocytes are expected to exhibit in vivo antitumour specificity and activity in patients, as they have done in animal models.
In an attempt to develop more competent gene-modified anti-tumour T cells we are working on introducing the same TCR genes into mouse haematopoietic stem cells (HSCs). It is anticipated that once these cells are transferred into recipient mice they will develop into T cells with the desired antitumour specificity. Tumour challenge experiments on recipient mice will then be performed, to study whether T cells that have developed in vivo from gene modified HSCs have antitumour activity and can confer tumour protection, without causing autoimmunity. Importantly, as the tumour-specific TCR we are using in this study recognises a self-antigen that is over-expressed in many leukaemias and solid tumours, this model will give us the opportunity to explore in detail central and peripheral tolerance mechanisms that naturally occur against T cells specific for tumour-associated, self antigens.
Stauss HJ, Cesco-Gaspere M, Thomas S, Hart DP, Xue SA, Holler A, Wright G, Perro M, Pospori C, King J, Morris EC (2007). Monoclonal T-cell receptors: new reagents for cancer therapy. Molecular Therapy 2007 Oct;15(10):1744-50.