Professor Andrew George
Molecular Immunotherapy Laboratory
Our work focuses on understanding the molecular process involved in immunological responses, and harnessing them for the treatment of disease.
Within this broad remit the laboratory has particular interests in corneal transplantation, in dendritic cells, in using antibodies to target gene therapy vectors and contrast agents for imaging, induction of tolerance and using mathematical and computer models to help understand the specificity of the immune system.
The cornea is the most commonly transplanted organ, with around 40 000 grafts performed every year in the USA alone. It is commonly thought that corneal grafts are not rejected, as the eye is an immune privileged site. However, this is not the case, and around a quarter of all grafts are lost within 4-5 years, in most cases due to immunological rejection of the cornea. In this laboratory, in work that is led by Andrew George and Frank Larkin, we are investigating the mechanisms by which the grafts are rejected, as well as devising methods to prevent or reduce rejection. This includes the administration of recombinant immunomodulatory proteins as well as gene therapy and vaccination with tolerogenic dendritic cells.
We have developed methods of using antibodies to target gene therapy vectors, including liposomes and dendrimers, to particular tissues. We have concentrated on vascular and corneal endothelium, and have shown specific delivery using antibodies directed against adhesion molecules. This allows specific delivery of the gene construct to activated endothelium.
Induction of tolerance
Allied to both the above areas is the use of genetic modification to induce tolerance. This offers the attractive prospect of being able to downregulate the immune response specifically to the graft, without causing generalised immunosuppression. We have developed methods to genetically modify dendritic cells (the cells responsible for initial activation of T cells) so that rather than activating T cells they render them tolerant. These strategies are being developed in collaboration with Giovanna Lombardi and Robert Lechler in King’s College London.
Work in our laboratory has been funded by
• Action Medical Research
• British Heart Foundation
• Arthritis and Rheumatism Council
• Wellcome Trust
For publications from our laboratory please see Andrew George's personal web page.
Beutelspacher SC, Tan PH, McClure MO, Larkin DFP, Lechler RI and George AJT (2006) Expression of indoleamine 2,3-dioxygenase (IDO) by endothelial cells: implications for the control of allosponses. Am J of Transplant 6: 1320-1330
Tan PH, Yates J, Xue SA, Jordan WR, Dong R, Ritter MA, Lechler RI, Lombardi G and George AJT (2005) Creation of tolerogenic antigen presenting cells via intracellular CTLA4: a novel strategy with potential clinical utility. Blood 106:2936-2943
Tan PH, Sagoo P, Chan C, Yates JB, Campbell J, Beutelspacher SC, Foxwell BMJ, Lombardi G and George AJT (2005) J Immunol 174:7633-7644
Tan PH, Beutelspacher SC, Xue S-A, Wang Y-H, Mitchell P, McAlister JC, Lar
kin DFP, McClure MO, Stauss HJ, Ritter MA, Lombardi G and George AJT (2005) Blood 105:3824-3832