       Document 1041
 DOCN  M9621041
 TI    Expression and characterization of CD4-IgG2, a novel heterotetramer that
       neutralizes primary HIV type 1 isolates.
 DT    9602
 AU    Allaway GP; Davis-Bruno KL; Beaudry GA; Garcia EB; Wong EL; Ryder AM;
       Hasel KW; Gauduin MC; Koup RA; McDougal JS; et al; Progenics
       Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
 SO    AIDS Res Hum Retroviruses. 1995 May;11(5):533-9. Unique Identifier :
       AIDSLINE MED/96093887
 AB    CD4-IgG2 is a novel fusion protein comprising human IgG2 in which the Fv
       portions of both heavy and light chains have been replaced by the V1 and
       V2 domains of human CD4. This tetrameric protein is being developed as
       an immunoprophylactic agent to reduce the probability of infection
       following HIV-1 exposure, in settings such as occupational or perinatal
       exposure to the virus. CD4-IgG2 has been expressed in Chinese hamster
       ovary cells and is secreted as a fully assembled heterotetramer. The
       protein binds with nanomolar affinity to purified gp120 from both a
       laboratory-adapted strain and a primary isolate of HIV-1.
       Pharmacokinetic studies in rabbits demonstrated that CD4-IgG2 has a
       plasma terminal half-life greater than 1 day, compared with 15 min for
       soluble CD4 (sCD4). CD4-IgG2 does not bind to Fc receptors on the
       surface of U937 monocyte/macrophage cells. Compared to molecules that
       incorporate the Fc portion of IgG1, CD4-IgG2 has less potential to
       mediate functions such as antibody-dependent enhancement of infection or
       transplacental transmission of HIV-1. When tested in a virus-free HIV-1
       envelope glycoprotein-mediated cell fusion assay, the tetrameric
       CD4-IgG2 molecule inhibited syncytium formation more effectively than
       monomeric sCD4 or a dimeric CD4-gamma 2 fusion protein. This suggests
       the protein will block cell-to-cell transmission of HIV-1. Moreover,
       CD4-IgG2 effectively neutralized a panel of laboratory-adapted strains
       and primary isolates of HIV-1, including strains with different tropisms
       and isolated from different stages of the disease, at concentrations
       that should be readily achieved in vivo.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY/PHARMACOKINETICS  CD4
       Immunoadhesins/*PHARMACOLOGY  CHO Cells  Giant Cells/VIROLOGY  Hamsters
       Human  HIV Infections/*PREVENTION & CONTROL  HIV-1/*DRUG EFFECTS
       Neutralization Tests  Rabbits  Recombinant Fusion
       Proteins/GENETICS/PHARMACOLOGY/  PHARMACOKINETICS  JOURNAL ARTICLE

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

