Inhibition of EphB4 Receptor Signaling by Ephrin-B2-Competitive and Non-Competitive DARPins Prevents Angiogenesis.

The receptor tyrosine kinase EphB4 is involved in tumor angiogenesis, proliferation, and metastasis. Designed ankyrin repeat proteins (DARPins) binding to the EphB4 extracellular domain were identified from a combinatorial library using phage display. Surface plasmon resonance (SPR) allowed us to distinguish between DARPins that either compete with the EphB4 ligand ephrin-B2 for binding to a common site or target a different epitope.

Expression of mutant non-cleavable Fas ligand on retrovirus packaging cells causes apoptosis of immunocompetent cells and improves prodrug activation gene therapy in a malignant glioma model.

Recombinant retroviruses (RV) have been widely used as vectors for clinical gene therapy of malignant brain tumors. Because of the very limited stability of these vectors in vivo, RV producing cells (VPC) are routinely used for intratumoral RV release. The host immune system, however, recognizes the intratumorally grafted allogeneic or xenogeneic VPC, and mounts an immune response against them.