Characterization of crystals of an antibody-recognition fragment of the cancer differentiation antigen mesothelin in complex with the therapeutic antibody MORAb-009.

The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the binding of mesothelin to CA-125 and displays promising anticancer potential. It is currently undergoing clinical trials. In order to understand the basis of the interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment of mesothelin (residues 7-64) were crystallized. The crystals of the Fab diffracted X-rays to 1.75 Å resolution and had the symmetry of space group P4(1)2(1)2, with unit-cell parameters a = b = 140.6, c = 282.0 Å. The crystals of the mesothelin-Fab complex diffracted to 2.6 Å resolution and belonged to the hexagonal space group P6(4), with unit-cell parameters a = b = 146.2, c = 80.9 Å. Structural analyses of these molecules are in progress.