Generation of a protective human monoclonal for the treatment of gram-negative sepsis.
Using a combination of Epstein-Barr virus transformation and cell fusion to a mouse/human heteromyeloma cell line, we have generated a human monoclonal antibody, D234, that recognizes cross-reactive determinants on the lipopoly-saccharides (LPS) of Gram-negative bacteria. Direct binding to a series of rough mutant LPSs and smooth LPSs demonstrates the broad cross-reactivity of this monoclonal. D234 inhibits Re LPS-induced chemiluminescence. In a murine model of Gram-negative sepsis, D234 given after infection significantly increases survival. This antibody may have therapeutic potential for the treatment of life-threatening Gram-negative infections in humans.
Larrick
J W
JW
Department of Immunology, Cetus Corporation, Palo Alto, California 94303.
Gray
O
O
Deinhart
T
T
Wang
J
J
Flatgaard
J
J
Chong
K T
KT
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D001424:Bacterial Infections / Q000628:therapy*; D003429:Cross Reactions; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides