Blocking EphB4 impedes angiogenesis and tumor growth

They report their data in the April 2010 issue of the American Journal of Pathology.

Angiogenesis is the growth of new blood vessels from pre-existing vessels. It is critical in the progression and development of malignant tumors. The receptor tyrosine kinase EphB4, which is expressed in many epithelial cancers, plays a key role in angiogenesis.

Krasnoperov et al have developed two monoclonal antibodies against EphB4 that inhibit angiogenesis and tumor growth by two distinct mechanisms. MAb131 inhibits endothelial tube formation in vitro (a sign of angiogenesis) and tumor growth in vivo by inducing degradation of human EphB4. In contrast, although mAb147 does not degrade EphB4, it inhibits angiogenesis and tumor growth of both EphB4+ and EphB4- tumors, likely by modulating the vascular response. As humanized versions of both of these antibodies maintain these tumor-inhibitory functions, antibodies against EphB4 are strong candidates for clinical applications.

Dr. Gill's group "describe[s] novel EphB4-specific monoclonal antibodies that inhibit formation and maturation of newly forming vessels and inhibit tumor growth in vivo. … [They suggest that] antibodies targeting the EphB4 pathway, therefore, have the potential to inhibit tumor growth via multiple mechanisms."

Krasnoperov V, Kumar SR, Ley E, Li X, Scehnet J, Liu R, Zozulya S, Gil PS: Novel EphB4 Monoclonal antibodies modulate angiogenesis and inhibit tumor growth. Am J Pathol 2010, 176 2029-2038.