Objective
The objective is to design two types of novel bioengineered IgG anti-Rhesus D moleculares:
- one for the prevention of immunisation against the Rhesus D;
- the other with the capacity to prevent the binding of harmful maternal antibodies to the Rh(D) antigen on fetal red cells.
These bioengineered IgG anti-D molecules can be produced at large scale by the biotechnology industry and will provide the EU with
- a safe and unlimited supply of anti-D for the prophylaxis of Rh(D) immunisation;
- a non-invasive therapy for the treatment of fetal anaemia caused by anti-D.
We will achieve our objective by the use of hybridoma technology, recombinant protein engineering, phage display technology, in vitro bioassays, transgenic mice (Rh mouse) and monkeys. The proposed project consists of three main parts, structure-function studies on i) the variable domains and ii) the constant domains of anti-D antibodies and iii) studies using animal models to assess the suitability of bioengineered IgG anti-D molecules for therapeutic use.
On the one hand the aim of the structure-function studies is to improve on the capacity of the bioengineered anti-D to clear Rh(D) positive red cells from the maternal circulation. On the other hand we expect to design an IgG anti-D molecule with a "novel" constant domain capable of being transported across the placenta but made incapable to recruit the classical Fc receptor (FcR) functions. Such a biologically "inactive" IgG anti-D preparation will compete with the maternal anti-D for binding and can thus prevent fetal anaemia. The principle of displacing harmful antibodies against blood cell antigens could also be applied to other immune-mediated cytopenia's of the blood.
It is proposed to investigate the use of mice transgenic for the Rh genes as a test model for the ability of the bioengineered antibodies to prevent immunisation against Rh(D).
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology immunisation
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine obstetrics
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Coordinator
2100 København
Denmark
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