Gene transfer of anti-gp41 antibody and CD4 immunoadhesin strongly reducesthe HIV-1 load in humanized severe combined immunodeficient mice

Objective: To study the anti-HIV-1 effects of the delivery of anti-gp41 mon oclonal antibody (mAb) and soluble CD4 (sCD4) immunoadhesin by genetically modified cells in HIV-l-infected, humanized severe combined immunodeficient (SCID) mice. Design: The complementary DNA of mAb 2F5, an anti-HIV-1 gp41 antibody, and of sCD4-Igc chimeric immunoadhesin were transferred into 3T3 cells using Mo loney murine leukaemia virus vectors. The cells were then incorporated into a collagen structure called the neo-organ, which allowed the continuous pr oduction of the therapeutic molecules. Methods: The antiviral effects in vivo of 2F5 or sCD4-lgG or both compounds were evaluated in neo-organ-implanted SCID mice that were grafted with hum an CD4 CEM T cells and challenged with HIV-I Lai or MN. Results: In SCID mice implanted with 2F5 neo-organs, antibody plasma levels reached 500-2000 ng/ml. Viral loads after HIV-1: challenge were significan tly reduced in neo-organ-implanted HIV-infected mice. Although 29 x 10(7) a nd 13 x 10(8) HIV-1-RNA copies/ml were detected at 12 days in the controls (mice injected with Lai and MN, respectively) less than 16.5 x 10(3) HIV-1- RNA copies/ml were observed in all implanted mice injected with either Lai or MN. The intracellular viral load was also reduced in CD4 cells recovered from the implanted mice. Comparable antiviral effects were obtained with C D4-IgC; neo-organs. Conclusion: Our results confirm the anti-HIV properties of 2F5 and sCD4-Igc continuously produced in vivo after ex-vivo gene therapy in SCID mice. (C) 2000 Lippincott Williams & Wilkins.