Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120

AIDS Res Hum Retroviruses. 1998 May 1;14(7):545-50. doi: 10.1089/aid.1998.14.545.

Abstract

A phase I dose escalation study was conducted with the human monoclonal anti-gp120 antibody F105, to evaluate the safety, pharmacokinetics, and functional activity of F105 in HIV-1-infected individuals. F105 is an IgG1(kappa) antibody reactive with a discontinuous epitope that overlaps the CD4-binding site of gp120. F105 neutralizes laboratory strains of HIV-1 and some primary isolates, and synergizes with other antibodies in neutralizing an expanded spectrum of isolates. Four patients each with CD4 counts between 200 and 500/mm3 received a single dose of F105 at 100 or 500 mg/m2, intravenously. Sustained levels of F105 were obtained in plasma, and there was no evidence of an immune response to F105 as determined by a double-antigen immunoassay. No patient experienced any toxicity. Infused antibody retained full functional activity as detected by the ability of sera to block the binding of labeled F105 to HIV-1-infected cells. Of note, all patients had preexisting antibody to the gp120 CD4-binding site. The ability to culture virus by quantitative microculture remained unchanged by this single dose of antibody. Thus, it can be concluded that F105 is safe and nontoxic as a single injection at the doses tested. Furthermore, the antibody retains full gp120-binding activity. In these patients, with preexisting CD4-binding site antibody, there is no evidence of anti-HIV-1 activity following a single antibody infusion.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Binding Sites
  • CD4 Antigens / metabolism
  • CD4 Lymphocyte Count
  • Female
  • Follow-Up Studies
  • HIV Antibodies / adverse effects
  • HIV Antibodies / immunology
  • HIV Antibodies / therapeutic use*
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV-1 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments