Prøveforelesning
Se prøveforelesningBedømmelseskomité
Dr. Bernard Maigret, LORIA, Nancy University, Frankrike
Professor Inger Sandlie, Institutt for molekylær biovitenskap, Universitetet i Oslo
Professor Carl Henrik Gørbitz, Kjemisk institutt, Universitetet i Oslo
Leder av disputas: Professor Tyge Greibrokk
Veileder: Ute Krengel, Ernesto Moreno
Sammendrag
World Health Organization (WHO) reported Cancer as the major cause of the death in 2007. Many different proteins, as well as other biomolecules have been identified as targets for the treatment of this disease. In this work we have given some insights to the possible mechanisms of action of four anti-tumor antibodies. Some of these antibodies are already in clinical trials with very promising results.
Three of the antibodies (14F7, P3 and 1E10) are related to a molecule that can only be found in tumor cells. This molecule is called N-glycolyl GM3. On the other hand Nimotuzumab targets a protein named epidermal growth factor factor, which is over-expressed by the tumor cells with an epithelial origin.
We obtained a theoretical model of how 14F7 and P3 antibodies bind to the N-glycolyl GM3 ligand, and for the 1E10 antibody is used as a vaccine, we proposed a mechanism that describes its ability to elicit antibodies which are able to recognize the N-glycolyl GM3 tumor-specific antigen.
The model of the Nimotuzumab-EGFR complex predicts a different inhibition mechanism of EGFR signaling by Nimotuzumab, as compared to other anti-EGFR antibodies. This may explain the lack of severe toxicity shown in the clinics for Nimotuzumab.
This results were achieved by the combination of experimental
and computational techniques. For example, protein crystallography, binding studies, molecular biology as well as computer simulations of molecular dynamics or docking.
This work has been the result of a fruitful collaboration between the Center of Molecular Immunology in Havana, Cuba and the Chemistry Department at the University of Oslo.
Kontaktperson
For mer informasjon, kontakt Raul Boris Briceno.