Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and nonseptic patients.
A mixture of five IgM human monoclonal antibodies (MAbs) against lipopolysaccharide antigens of Pseudomonas aeruginosa, plus a human IgG1 MAb against exotoxin A, were studied in 12 noninfected patients and 8 patients with P. aeruginosa bacteremia or pneumonia (or both). The preparation was well tolerated over a dose range of 0.3-1.2 ml/kg (0.75-3.0 mg/kg IgM protein). After a single infusion of 1.2 ml/kg (3.0 mg/kg IgM protein), serum antibody titers were boosted into therapeutic range, with serum half-lives ranging from 34 to 99 h. Also, opsonophagocytic activity in serum rose more than 1 log10 for all but one antibody. In no patient was an immunologic response against the MAb preparation detected.
Saravolatz
L D
LD
Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
Markowitz
N
N
Collins
M S
MS
Bogdanoff
D
D
Pennington
J E
JE
D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004361:Drug Tolerance; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009895:Opsonin Proteins; D010587:Phagocytosis; D011014:Pneumonia / Q000628:therapy*; D011552:Pseudomonas Infections / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018805:Sepsis / Q000628:therapy*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D009895:Opsonin Proteins