XENOTRANSPLANTATION: Strategies for the prevention of carbohydrate related (hyperacute) rejection

• Research unit: EU RFP
• Project number: 97.0369

Key words (English)

Xenotransplantation; carbohydrate antigens; anti-carbohydrate antibodies; complement

Alternative project number (English)

EU project number: BIO4CT972242

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.1 Biotechnology

Short description (English)

See abstract

Partners and International Organizations (English)

University of Göteborg (S), INSERM U 504, Paris (F), Free University of Amsterdam (NL), CERMAV, Grenoble (F), ITERT Nantes (F), Leiden University Medical Center (NL), Huddinge Hospital, Stockholm (S), SYNTESOME GmbH, Munich/ Moscow, GLYCOREX Ltd., Lund (S)

Abstract (English)

In pig to man transplantation, hyperacute rejection occurs mainly as the result of the reaction between carbohydrate antigens, expressed on endothelial cells of the pig organ, and preformed anti-carbohydrate antibodies of the recipient. A major target of these human natural antibodies is the disaccharide Gala1->3Gal. The project is focussed on strategies to block carbohydrate dependent rejections in xenotransplantation.
Our present view is that the disarming of only one of the several pathogenic routes of xenorejection will not be sufficient to ensure success. The binding of anti-carbohydrate antibodies is followed by complement activation and cell mediated events at later stages. All these different rejection events require specific approaches for their prevention. In this perspective we will combine a number of different strategies for prevention of xenograft rejection. We envisage the combination of strategies to block complement activation with the use of synthetic antigens - either as soluble substances or as immunoabsorption materials - to block the carbohydrate-mediated (hyperacute) rejection. Synthetic carbohydrates, such as oligo- or polymeric, sialylated Lewis x and Lewis a antigens will also be tested for blocking of leukocyte adhesion to endothelial cells.
The proposal is unique with regard to the biotechnological preparation of sugar-based compounds to control immune xenoreactivity, and the development of direct clinical tests and animal models to assess their efficacy. Also the development and biological testing of different strategies for achieving low expression of relevant sugar-dependent xenoantigens are of importance. Research on xenotransplantation is a transdisciplinary activity with an extreme breadth and width. This project encompasses basic and applied molecular biology, basic structural chemistry and biochemistry, immunohistochemistry, genetics, basic and applied physiology, animal and human experiments, as well as science of ethics and popular science documentation.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 97.0369