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Related Experiment Videos

CD4 immunoadhesins in anti-HIV therapy: new developments.

S M Chamow1, A M Duliege, A Ammann

  • 1Genentech, Inc., South San Francisco, CA 94080.

International Journal of Cancer. Supplement = Journal International Du Cancer. Supplement
|January 1, 1992
PubMed
Summary

Engineered CD4-IgG, a fusion protein, shows promise in preventing human immunodeficiency virus (HIV) infection and is safe for human use. Its placental transfer capability offers potential for preventing newborn HIV transmission.

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Area of Science:

  • Immunology
  • Virology
  • Biotechnology

Background:

  • CD4 is the primary cell-surface receptor for human immunodeficiency virus (HIV).
  • The V1 extracellular domain of CD4 is sufficient for HIV binding.
  • Soluble CD4 receptors have limitations in therapeutic applications.

Purpose of the Study:

  • To engineer a novel CD4-based therapeutic, CD4-IgG, for anti-HIV treatment.
  • To evaluate the in vivo efficacy, safety, and pharmacokinetic properties of CD4-IgG.
  • To explore the potential of CD4-IgG in preventing mother-to-child HIV transmission.

Main Methods:

  • Engineered a fusion protein (CD4-IgG) combining CD4 domains (V1 and V2) with human IgG Fc regions.
  • Assessed CD4-IgG efficacy in chimpanzees infected with HIV-1 IIIB.

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  • Evaluated placental transfer in rhesus monkeys and conducted a Phase I clinical trial in human patients with AIDS and AIDS-related complex.

    • Main Results:

    • CD4-IgG demonstrated protection against HIV-1 IIIB infection in chimpanzees when given pre-exposure.
    • Efficient placental transfer of CD4-IgG was observed in rhesus monkeys.
    • Phase I clinical trial showed CD4-IgG was well-tolerated in humans at doses up to 1000 µg/kg, with no significant toxicities.

    Conclusions:

    • CD4-IgG is a promising therapeutic candidate with enhanced properties over soluble CD4, including extended half-life and effector functions.
    • The ability of CD4-IgG to cross the placenta suggests its potential utility in preventing perinatal HIV transmission.
    • Further clinical development of CD4-IgG is warranted, particularly for preventing newborn HIV infection via maternal-fetal transfer.