Combination fusion protein therapy of refractory XXXX : demonstration of efficacy in cell culture.

@entity1 @entity137 @entity4047 @entity1313 @entity5 @entity245 @entity11 @entity816 @entity463
@entity1313 including @entity816 and @entity463 multiforme are difficult to treat because of their locally invasive nature and relative resistance to chemotherapy and radiation therapy. Novel agents that can kill multi-drug resistant @entity5 cells and reach @entity5 cells at distant sites in the brain are needed. One such class of agents is fusion proteins which consist of @entity1313 -selective peptide ligands fused to peptide toxins. The ligand directs the protein to the @entity11 cell surface; the peptide toxin is then internalized into the cell, translocates to the cytosol and catalytically inactivates protein synthesis leading to cell death. Fusion proteins are toxic to multi-drug resistant @entity1313 cells. Because of the large molecular weight of these molecules, a unique delivery system has been @entity245 ( @entity245 ). The method creates a bulk flow which supplements diffusion and achieves drug concentrations in the brain parenchyma orders of magnitude greater than by systemic administration. @entity1 with recurrent @entity11 treated with individual fusion protein @entity245 have obtained clinical remissions lasting years. However, @entity137 to normal brain have been observed and relapses ultimately occurred. To address the clinical need of these @entity1 and improve upon the therapeutic index observed to date with single fusion protein @entity245 , we generated a novel fusion protein DAB389EGF and tested it in combination with another active fusion protein, @entity4047 PE38QQR. We observed potent @entity137 with each fusion protein and synergistic @entity137 with the combination. Further, @entity1313 cells showed heterogeneous expression of individual receptors suggesting that the combination--DAB389EGF and IL13PE38QQR may show improved efficacy and should undergo further preclinical development for therapy of @entity1 with relapsed high-grade @entity11 .
