Related Experiment Videos
The in vivo and in vitro characterisation of an engineered human antibody to E-selectin
Background:
E-selectin is an endothelial cell specific adhesion molecule that is believed to play an important role in the early stages of leukocyte extravasation.
Objectives:
Here we describe the construction and evaluation of an engineered human monoclonal antibody that blocks E-selectin function.
Results:
SPLAT-1 is an engineered human monoclonal antibody that has a very similar affinity for E-selectin as its murine parent antibody. In vitro SPLAT-1 blocks the binding of human leukocytes to E-selectin and does not mediate antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated lysis of endothelial cells. In vivo, SPLAT-1 inhibits the recruitment of leukocytes to cytokine-inflamed human skin grafted on to SCID mice and has a long circulating half-life in primates. It does not appear to provoke an immune response in primates even on repeat administration.
Conclusions:
SPLAT-1 has the characteristics of a antibody suitable for human therapy studies.