Document 0660
 DOCN  M9490660
 TI    Plasma pharmacokinetics and biological activity of a human
       immunodeficiency virus type 1 neutralizing human monoclonal antibody,
       F105, in cynomolgus monkeys.
 DT    9411
 AU    Cavacini LA; Power J; Emes CL; Mace K; Treacy G; Posner MR; Department
       of Medicine, New England Deaconess Hospital, Harvard; School of
       Medicine, Boston, Massachusetts 02215.
 SO    J Immunother Emphasis Tumor Immunol. 1994 May;15(4):251-6. Unique
       Identifier : AIDSLINE MED/94340180
 AB    The IgG1 kappa human monoclonal antibody (HMab), F105 reacts with a
       discontinuous epitope on the CD4 binding site (CD4BS) of human
       immunodeficiency virus type 1 (HIV-1)/gp120 and has broad neutralizing
       activity. F105 HMab (60 mg/kg bolus) was administered intravenously to
       four monkeys and serum was collected at intervals to determine
       pharmacokinetics in a primate model. Average serum F105 concentrations,
       as determined by enzyme-linked immunosorbent assay, were analyzed with
       MINSQ software using a two-compartment, first-order model. The half-life
       for the alpha phase of the distribution curve is 6.7 h and for the beta
       elimination phase, 9.6 days. The volume of distribution is 0.65 L/kg and
       the rate of clearance 2 ml/kg/h. Serum levels of 1.3-1.6 mg/ml of F105
       were maintained for 24 h. When monkey serum from day 15 postdose was
       tested, total serum F105 was 230 +/- 79 micrograms/ml and was
       immunoreactive with cells infected with the MN and IIIB strains of HIV-1
       as determined by flow cytometry. Binding activity was identical to that
       obtained with stock F105 HMab. Identical neutralizing activity between
       the injected and uninjected antibody was also observed. Thus, serum
       neutralizing titers (90%) of 1:2000 at peak and 1:30 at day 15 postdose
       for MN virus were observed. These data indicate that high in vivo levels
       of HMab F105 can be attained by single bolus administration with full
       retention of biological activity. Of importance, levels of antibody
       necessary for effective neutralization can be achieved and maintained.
 DE    Animal  Antibodies, Monoclonal/*BLOOD/*IMMUNOLOGY  Enzyme-Linked
       Immunosorbent Assay  Female  Human  HIV Antibodies/*BLOOD/*IMMUNOLOGY
       HIV Infections/IMMUNOLOGY  HIV-1/*IMMUNOLOGY  Macaca fascicularis  Male
       Neutralization Tests  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).