Pancreatic cancer is diagnosed 60,000 times in the USA and the EU each year; the same number of people die of this disease each year. This illustrates that existing therapies have little effect once the disease is diagnosed; survival time is 80 to 160 days. Gastrin drives the tumor growth. Recently, an anti-gastrin vaccine was developed able to double the survival time and to improve the quality of life of pacreatic cancer patients. Unfortunately, only a limited number of individuals respond to the vaccine and produce antibodies; even then development of antibodies is slow. We propose an alternative which will take effect immediately in all individuals treated. To this end, we propose to develop high affinity and low cost synthetic antibodies -'binding bodies'- against gastrin. Binding bodies are two or more CDR-based peptides (CDR's are the hypervariable regions of the antigen-interaction site of an antibody) coupled covalently to a small synthetic scaffold. The concept works: ample evidence shows that CDR-based peptides can bind antigen. Recent data (PS,1) show that combinations of 2 CDR-based peptides give much higher binding and much more specificity. We speculate that further optimisation yield low cost synthetic antibodies -binding bodies- with activities similar to natural antibodies.To sort this out the integration of six different technologies is required: 1.recombinant antibody libraries to define CDR-based peptides binding gastrin (CNIO,2), 2.bio-informatic approach to the prediction of optimized set of binding bodies (AN,4), 3.peptide synthesis and supramolecular design of optimized binding body libraries (PS,1), 4. affinity measurements to validate antibody and binding bodies (ULP,3), 5. animal models to validate therapeutic potential of anti-gastrin binding bodies (UMCU,6), 6. binding body arrays for clinical applications (proteom,5). It goes without saying that success of this project can only be obtained by this multi-disciplinary approach.
Funding SchemeCooperative - SMEs-Co-operative research contracts