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.
journal_name
Naturejournal_title
Natureauthors
Caskey M,Klein F,Lorenzi JC,Seaman MS,West AP Jr,Buckley N,Kremer G,Nogueira L,Braunschweig M,Scheid JF,Horwitz JA,Shimeliovich I,Ben-Avraham S,Witmer-Pack M,Platten M,Lehmann C,Burke LA,Hawthorne T,Gorelick RJ,Walkdoi
10.1038/nature14411subject
Has Abstractpub_date
2015-06-25 00:00:00pages
487-91issue
7557eissn
0028-0836issn
1476-4687pii
nature14411journal_volume
522pub_type
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