title: Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120.
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.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Cavacini
authors.forename: M H
authors.initials: MH
authors.lastname: Samore
authors.forename: J
authors.initials: J
authors.lastname: Gambertoglio
authors.forename: B
authors.initials: B
authors.lastname: Jackson
authors.forename: M
authors.initials: M
authors.lastname: Duval
authors.forename: A
authors.initials: A
authors.lastname: Wisnewski
authors.forename: S
authors.initials: S
authors.lastname: Hammer
authors.forename: C
authors.initials: C
authors.lastname: Koziel
authors.forename: C
authors.initials: C
authors.lastname: Trapnell
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments