mutations increase variable new-antigen receptor single-domain antibodies for VEGF neutralization.

The stability, binding, and tissue penetration of variable new-antigen receptor (VNAR) single-domain antibodies have been tested as part of an investigation into their ability to serve as novel therapeutics. V13 is a VNAR that recognizes vascular endothelial growth factor 165 (VEGF). In the present study V13 was used as a parental molecule into which we introduced mutations designed . Two of the designed VNAR mutants were expressed, and their ability to recognize VEGF was assessed and . One mutation (Pro98Tyr) was designed to increase VEGF recognition, while the other (Arg97Ala) was designed to inhibit VEGF binding. Compared to parental V13, the Pro98Tyr mutant showed enhanced VEGF recognition and neutralization, as indicated by inhibition of angiogenesis and tumor growth. This molecule thus appears to have therapeutic potential for neutralizing VEGF in cancer treatment.