CONTINUOUS SECRETION OF HUMAN SOLUBLE CD4 IN MICE TRANSPLANTED WITH GENETICALLY-MODIFIED CELLS

Somatic transgenesis can be used to confer endogenous production of pr oteins with therapeutic properties. One such product, recombinant solu ble human CD4 (sCD4), has been shown to be an efficient inhibitor of h uman 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 a nd synthetic fibers coated with basic fibroblast growth factor and imp lanted in the peritoneal cavity of syngeneic mice. implantation of suc h sCD4-secreting organoids into cyclosporin A-treated CH3 mice elicite d a strong antibody response against sCD4. Implantation of sCD4-secret ing organoids into immunotolerant mice (transgenic for transmembrane h uman CD4) resulted in continuous sCD4 production, detected during 60-d ays in animal sera. The Serum levels obtained were significant, but to o limited as yet for anti-HIV purposes. Nevertheless, this model may b e of interest in various fields, as. it provides the first demonstrati on that one potentially therapeutic protein, despite its half-life of a few hours, could remain present in vivo 2 months after a single soma tic transgenesis.