The in vivo and in vitro characterisation of an engineered human antibody to E-selectin.

Journal article

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.

Authors: Owens, R; Ball, E; Ganesh, R; Nesbitt, A; Brown, D

• Publication status: Published
• Journal: Immunotechnology : an international journal of immunological engineering
• Volume: 3
• Issue: 2
• Pages: 107-116
• Publication date: 1997-06-01
• DOI: 10.1016/s1380-2933(97)00066-3
• ISSN: 1380-2933
• Language: English
• Keywords: Humans; Antibodies, Monoclonal; Mice; Animals; Half-Life; Female; Protein Engineering; E-Selectin; Macaca fascicularis; Injections, Intravenous; Male