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.


OBJECTIVE
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.
Owens
R
R
Celltech Therapeutics, Slough, UK.
Ball
E
E
Ganesh
R
R
Nesbitt
A
A
Brown
D
D
Gofton
C
C
Stephens
S
S
Chaplin
L
L
Christofidou-Solomidou
M
M
Blake
S
S
Howat
D
D
Buurman
W A
WA
Albelda
S
S
Robinson
M K
MK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D019040:E-Selectin / Q000276:immunology*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D015202:Protein Engineering
D000911:Antibodies, Monoclonal; D019040:E-Selectin