Anti-idiotypic vascular endothelial growth factor antibodies and their use as medicaments

Abstract

An anti-idiotypic vascular endothelial growth factor antibody, an Fab fragment, and pharmaceutical compositions thereof, being ligands of the human KDR receptor or of the murine flk-1 receptor and not a ligand of fit are provided.

1 . Method for diagnosis or treatment of pathologies involving endothelial cells engaged in an angiogenesis process, comprising administering an effective amount of an anti-idiotypic vascular endothelial growth factor antibody which is circulating, targets angiogenic endothelial cells and is a ligand of the human KDR receptor or of the murine flk-1 receptor, without affecting quiescent endothelial cells, wherein said antibody is not a ligand of flt.  
     
     
         2 . Method according to  claim 1  for treatment of pathologies involving endothelial cells engaged in an angiogenesis process, without affecting quiescent endothelial cells wherein the anti-idiotypic antibody is coupled to a toxin, the function for which is to block translation of proteins, or coupled to a radioactive element or which anti-idiotypic antibody is in the form of a Fab fragment.  
     
     
         3 . Method according to  claim 1  for treatment of pathologies involving endothelial cells engaged in an angiogenesis process, to promote angiogenesis, without affecting quiescent endothelial cells.  
     
     
         4 . Method according to  claim 2 , in which the antibody is coupled to a toxin chosen from saporin and ricin or a radioactive element, such as iodine-125 or -131.  
     
     
         5 . Method for stimulation of physiological angiogenesis, increasing the speed of formation of blood vessels in the course of cicatrization or maturation of the corpus luteum of the ovary, or for stimulation of angiogenesis in the course of obstructive pathologies of vessels, in order to reperftuse regions rendered ischemic during vascular thrombosis, comprising administering to a patient in need of such treatment an effective amount of anti-idiotypic antibodies that are ligands of the human KDR receptor or the murine flk-1 receptor and not ligands of flt.  
     
     
         6 . Method for treatment of pathologies requiring inhibition of angiogenesis, comprising administering to a patient in need of such treatment an effective amount of anti-idiotypic antibodies associated with a toxin or a radioactive element or of the Fab fragment of anti-idiotypic antibodies, said antibodies being ligands of the human KDR receptor or the murine flk-1 receptor and not ligands of flt.  
     
     
         7 . Method according to  claim 1  for diagnosis of pathologies involving endothelial cells engaged in an angiogenesis process.  
     
     
         8 . Process for the preparation of an anti-idiotypic antibody, comprising: 
 a) injecting purified VEGF into a rabbit,    b) withdrawing blood to recover purified Ig containing specific anti-VEGF IgG, and then in an optional stage the specific anti-VEGF IgG are purified from the purified Ig,    c) injecting said purified Ig or said purified anti-VEGF IgG into the popliteal ganglions of a rabbit of the same origin as that used for injection of the VEGF,    d) withdrawing blood to recover the total Ig, for example by protein A, and then to subject the total Ig to two immunoadsorptions:    (i) an immunoadsorption on an affinity column prepared with the pre-immune Ig of the rabbit which has been used to produce the anti-VEGF IgG, to eliminate the anti-allotypic or isotypic antibodies,    (ii) an immunoadsorption on an affinity column prepared with the anti-VEGF IgG, to purify the anti-idiotypes.