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Session 58 Poster Session Entry Inhibitors Session Time: 4:30-6:30 pm Room 4E-F

401-T. PRO 542 (CD4-IgG2) has a Profound Impact on HIV-1 Replication in the Hu-PBL-SCID Mouse Model M. Franti*1, T. O’Neill2, P. Maddon2, D. R. Burton1, P. Poignard1, and W. Olson2 1Scripps Res. Inst., La Jolla, CA and 2Progenics Pharmaceuticals, Inc., Tarrytown, NY Background: PRO 542 is a recombinant antibody-like fusion protein wherein the D1D2 domains of human CD4 are grafted onto the heavy and light chain constant regions of human IgG2. Unlike monovalent and divalent CD4-based proteins, tetravalent CD4-IgG2 broadly and potently neutralizes primary HIV-1 isolates. We have evaluated the in vivo anti-viral activity of PRO 542 using the hu-PBL-SCID mouse model of HIV infection. Methods: SCID mice were reconstituted with normal human peripheral blood mononuclear cells and infected 2 weeks later with HIV-1JR-CSF, a primary CCR5-using virus. When viral steady state was reached (~10 days post-infection), animals were treated intraperitoneally or subcutaneously with varying doses of PRO 542. Plasma viral loads were monitored pre- and post-injection by quantitative RT-PCR (Amplicor assay). Results: Viral loads fell by as much as 10-fold to undetectable levels (<400 copies/mL) in each of the 5 PRO 542-treated animals and then returned to baseline levels following cessation of PRO 542 therapy. In contrast, viral loads remained steady throughout the treatment period in control animals. Conclusions: In contrast to the best available neutralizing monoclonal antibodies to gp120 and gp41, PRO 542 demonstrated potent therapeutic activity in the hu-PBL-SCID mouse model of HIV infection. Future studies in this model will further explore the activity of PRO 542 used alone and in combination with other classes of HIV-1 entry inhibitors.

©2002 9th Conference on Retroviruses and Opportunistic Infections