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Nature. 2015 Jun 25;522(7557):487-91. doi: 10.1038/nature14411. Epub 2015 Apr 8.

Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
3
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
4
1] First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany [2] Clinical Trials Center Cologne, ZKS Köln, BMBF 01KN1106, University of Cologne, Cologne, Germany.
5
1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
6
1] First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany [2] German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
7
1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Division of Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10065, USA.
8
Celldex Therapeutics, Inc., Hampton, New Jersey 08827, USA.
9
AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
10
Ragon Institute of MGH, MIT and Harvard, Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
11
Division of Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10065, USA.
12
1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.

Abstract

HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

PMID:
25855300
PMCID:
PMC4890714
DOI:
10.1038/nature14411
[Indexed for MEDLINE]
Free PMC Article

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