Newsletter - Edition 29
Reprogramming the Immune System
Oxford Innovation Society Lecture - September 1999
Professor Herman Waldmann, Sir William Dunn School of Pathology
There are a wide range of diseases which currently are managed by long-term immunosuppression. These range from auto-immune diseases such as rheumatoid arthritis to control of transplant rejection. However, long-term immunosuppression carries risks of infection, and other drug-mediated side-effects. One of the major therapeutic goals in the field of Immunology is to be able to re-educate or re-programme the immune system so that it can avoid attacking tissues through its own natural processes. In practice this would mean offering short-term therapy to achieve a long-term benefit.
After all our immune systems have learned to identify what is "self" by acquired processes, and have inactivated potentially aggressive lymphocyte clones in normal development through a range of mechanisms that Professor Waldmann outlined in his talk.
A key cell in immune reactions is the thymus-processed or T-cell. No immune response can occur unless T-cells get involved. T-cells need to collaborate with each other so as to be able to initiate clonal expansion and differentiation into destructive effector cells. This begins with T-cells with receptors for the antigen coming together on the surface of specialised antigen-presenting cells called "dendritic-cells". If sufficient T-cells encounter an antigen-presenting dendritic cell, then that dendritic cell gets activated, and in-turn send signals to the T-cells to grow. If the dendritic cell is not activated the T-cells may get signals to become inactivated and even die.
It has proven possible to interfere with T-cell collaboration with each other and with dendritic cells using antibodies which block attachment of T-cells to the dendritic cell, or which reduce the numbers of T-cells. Pre-clinical studies have shown that this can result in tolerance both to transplanted tissues, and in models of auto-immune disease.
The principles that emerge from these studies have now been applied to the Clinic through provision of antibodies by the Oxford Therapeutic Antibody Centre which was established by Dr Geoffrey Hale and Professor Herman Waldmann for the purposes of producing clinical grade antibody for therapy. In collaboration with Professor RY Calne in Cambridge it has been possible to show that antibody-mediated reduction of T-cell numbers in patients receiving the antibody CAMPATH-1H, allowed management of recipients with just half-dose cyclosporine A, without the need for steroids or azathioprine. This finding in a study conducted on 31 patients offers new hope for the prospect of achieving immunological-tolerance in organ transplantation.
*CAMPATH-1H is a trademark of LeukoSite Inc.
Newsletter - Edition 29 Contents
- Monoclonal Antibodies
- Reprogramming the Immune System
- Oxford Gene Technology
- Isis College Fund
- Oxagen Ltd