Document 0855
 DOCN  M95A0855
 TI    Continuous secretion of human soluble CD4 in mice transplanted with
       genetically modified cells.
 DT    9510
 AU    Valere T; Bohl D; Klatzmann D; Danos O; Sonigo P; Heard JM; Institut
       Cochin de Genetique Moleculaire (ICGM-CNRS UPR415),; Paris, France.
 SO    Gene Ther. 1995 May;2(3):197-202. Unique Identifier : AIDSLINE
       MED/95339005
 AB    Somatic transgenesis can be used to confer endogenous production of
       proteins with therapeutic properties. One such product, recombinant
       soluble human CD4 (sCD4), has been shown to be an efficient inhibitor of
       human immunodeficiency virus 1 (HIV-1) in vitro, but its too short
       half-life in vivo has impaired long-term clinical trials in AIDS
       patients. Using a retroviral vector, we introduced the cDNA of sCD4 into
       primary mouse fibroblasts. The cells were enclosed in a lattice of
       collagen and synthetic fibers coated with basic fibroblast growth
       factor, and implanted in the peritoneal cavity of syngeneic mice.
       Implantation of such sCD4-secreting organoids into cyclosporin A-treated
       C3H mice elicited a strong antibody response against sCD4. Implantation
       of sCD4-secreting organoids into immunotolerant mice (transgenic for
       transmembrane human CD4) resulted in continuous sCD4 production,
       detected during 60 days in animal sera. The serum levels obtained were
       significant, but too limited as yet for anti-HIV purposes. Nevertheless,
       this model may be of interest in various fields, as it provides the
       first demonstration that one potentially therapeutic protein, despite
       its half-life of a few hours, could remain present in vivo 2 months
       after a single somatic transgenesis.
 DE    Animal  Antibodies/BLOOD  Antigens,
       CD4/*BIOSYNTHESIS/BLOOD/GENETICS/IMMUNOLOGY  Cyclosporine
       Fibroblasts/TRANSPLANTATION  *Gene Transfer  Genetic Vectors/GENETICS
       Human  Immunosuppression  Male  Mice  Mice, Inbred C3H  Mice, Inbred
       C57BL  Mice, Transgenic  Moloney Leukemia Virus/GENETICS
       Organoids/TRANSPLANTATION  Recombinant
       Proteins/BIOSYNTHESIS/BLOOD/GENETICS/IMMUNOLOGY  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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