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CD4 SECOND GENERATION HYBRID HALF-LIFE

Executive Summary

CD4 SECOND GENERATION HYBRID HALF-LIFE may extend to a week or more compared to a half-hour for the first generation substance, New England Deaconess Hospital Hematology Chief Jerome Groopman, MD, told a March 1 biotechnology conference in Chicago. "It turns out that the half-life of the ]second generation[ chimeric protein is determined by the antibody half-life, which in terms of the hybrid may exist within the plasma for a week or more," Groopman said, versus 30 minutes to an hour for the first generation CD4. The conference was sponsored by Communitech and Vector Securities. Results with the fused CD4/Immunoglobulin G (IgG) product were published in the Feb. 11 issue of Nature. Genentech's Daniel Capon, NCI Director Samuel Broder and Groopman reported that the chimeric CD4 neutralized all forms of the Human Immunodeficiency Virus in vitro and did not seek to destroy "bystander" healthy cells. First generation CD4 products developed by Genentech, Biogen, and SmithKline are all currently in Phase I. Results from those studies could be presented in June at the International AIDS conference in Montreal. Biogen recently announced that it has a second generation CD4 product in development ("The Pink Sheet" Feb. 27, p. 6). Referring to potential advantages of the hybrid CD4 product, Groopman noted that "antibodies ]like IgG[ are actively transported across various tissues and in various organs, most notably the placenta." This may "afford a way" to either treat an infected fetus or to protect it from the AIDS virus, Groopman said. The hybrid CD4, due to its antibody properties, is also able to stimulate the production of killer white cells which target the HIV infected cells in a process called Antibody Dependent Cellular Cytotoxicity (ADCC). One concern researchers have had about CD4 is the fact that 20% of HIV infected individuals carry antibodies to the molecule. The antibodies "still theoretically could pose a problem to the first generation material," Groopman noted, whereas "it turns out that they don't recognize the second generation material." However, since the beginning of Phase I trials in August with soluble CD4, "we have not seen antibody against the recombinant protein," Groopman pointed out.

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