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Antibodies cross-reactive with E- and P-selectin block both E- and P-
selectin functions
EL Berg, C Fromm, J Melrose and N Tsurushita
Protein Design Labs, Inc. Mountain View, CA 94043.
E- and P-selectin are inflammation-induced cell adhesion molecules that
mediate leukocyte-endothelial cell and leukocyte-platelet interactions.
Monoclonal antibodies (MoAbs) specific for either E-selectin or P- selectin
are protective in several animal models of inflammatory disease. To
generate an MoAb with broader therapeutic potential, MoAbs that bind to
both E- and P-selectin were generated by immunization of mice with mouse
pre-B cell lines transfected with human E- and P- selectin. Interestingly,
although the only selection criterion was the ability to bind both E- and
P-selectin, all three antibodies obtained efficiently block both E- and
P-selectin-mediated functions. The inhibited functions include neutrophil
or HL-60 cell binding to tumor necrosis factor-alpha-activated human
umbilical vein endothelial cells, E- or P-selectin transfectant cell lines,
and platelet-HL-60 rosetting. These antibodies, EP-5C7, EP-2C9, and EP-1D8,
recognize the same or overlapping epitope within the lectin domains of E-
and P-selectin. The data suggest that functionally important epitopes of
homologous proteins can be targeted by selecting for antibodies with
reactivity toward both proteins. Furthermore, a potent blocking antibody
specific for both E- and P-selectin may provide a more effective and
broadly useful reagent for treating acute and potentially certain chronic
inflammatory conditions.
Volume 85,
Issue 1,
pp. 31-37,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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