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

Article

关键词: MONOCLONAL-ANTIBODIES;    HIV-1 NEUTRALIZATION;    GENETIC-DETERMINANTS;    PASSIVE TRANSFER;    IN-VIVO;    THERAPY;    VIRUS;    IMMUNOTHERAPY;    VACCINE;    MICE;   

DOI  :  10.1038/nature14411

来源: SCIE

【 摘 要 】

HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned(1-3). 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(6-10). 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(11), in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log(10) 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.

【 授权许可】

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