title: Mouse/human chimeric anti-HIV-1 gp120 antibody to the principal neutralizing determinant: tolerability and pharmacokinetics in cynomolgus monkeys, Macaca fascicularis.
abstract: In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47,439 in HIV-1 infected individuals, it was administered to Macaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47,439/kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T1/2 alpha of 14.2 h (range 11.8-19.3 h) and a mean T1/2 beta of 172.6 h (range 137.2-220.5h). Following four successive antibody infusions serum concentrations of CGP 47,439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients.
authors.affiliation: Tanox Biosystems, Inc., Houston, TX 77025.
authors.forename: R S
authors.initials: RS
authors.lastname: Liou
authors.forename: M S
authors.initials: MS
authors.lastname: Fung
authors.forename: U
authors.initials: U
authors.lastname: Zühlke
authors.forename: F
authors.initials: F
authors.lastname: Gudat
authors.forename: S
authors.initials: S
authors.lastname: McKinney
authors.forename: W
authors.initials: W
authors.lastname: Gordon
authors.forename: W
authors.initials: W
authors.lastname: Bee
authors.forename: L
authors.initials: L
authors.lastname: Botta
authors.forename: D
authors.initials: D
authors.lastname: Gygax
authors.forename: T W
authors.initials: TW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D011993:Recombinant Fusion Proteins