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

机译：通过广泛中和抗体3BNC117在HIV-1感染者中抑制病毒血症

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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.
机译：结合第一代单克隆抗体的HIV-1免疫疗法在临床前和临床环境中大多无效，因此被放弃（1-3）。但是，最近开发的基于单细胞的抗体克隆方法已经发现了针对HIV-1的新一代更有效的广泛中和抗体（参考文献4、5）。这些抗体可以预防人源化小鼠和非人类灵长类动物的感染并抑制病毒血症，但尚未评估其在人类HIV-1免疫疗法中的潜力（6-10）。在这里，我们报告了3BNC117（一种有效的人CD4结合位点抗体（11））在未感染者和HIV-1感染者中的第一人称剂量升级1期临床试验的结果。 3BNC117输液耐受性良好，并显示出良好的药代动力学。一次输注3BNC117的30mg kg（-1）可使HIV-1感染者的病毒载量降低0.8-2.5 log（10），病毒血症持续28天仍显着降低。抗性病毒株的出现是可变的，一些个体对3BNC117保持敏感28天。我们得出的结论是，作为单一药物，3BNC117在减少HIV-1病毒血症方面是安全有效的，因此应该探索免疫疗法作为预防，治疗和治愈HIV-1的新方法。

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  • 来源
    《Nature》 |2015年第7557期|487-491|共5页
  • 作者

    Caskey Marina; Klein Florian; Lorenzi Julio C. C.; Seaman Michael S.; West Anthony P. Jr.; Buckley Noreen; Kremer Gisela; Nogueira Lilian; Braunschweig Malte; Scheid Johannes F.; Horwitz Joshua A.; Shimeliovich Irina; Ben-Avraham Sivan; Witmer-Pack Maggi; Platten Martin; Lehmann Clara; Burke Leah A.; Hawthorne Thomas; Gorelick Robert J.; Walker Bruce D.; Keler Tibor; Gulick Roy M.; Faetkenheuer Gerd; Schlesinger Sarah J.; Nussenzweig Michel C.;

  • 作者单位

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Harvard Univ, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA;

    CALTECH, Div Biol, Pasadena, CA 91125 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany|Univ Cologne, Clin Trials Ctr Cologne, ZKS Koln, D-50931 Cologne, Germany;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA|Univ Freiburg, D-79085 Freiburg, Germany;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany|Partner Site Bonn Cologne, German Ctr Infect Res DZIF, Cologne, Germany;

    Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany|Partner Site Bonn Cologne, German Ctr Infect Res DZIF, Cologne, Germany;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA|Cornell Univ, Div Infect Dis, Weill Med Coll, New York, NY 10065 USA;

    Celldex Therapeut Inc, Hampton, NJ 08827 USA;

    Frederick Natl Lab Canc Res, Leidos Biomed Res, AIDS & Canc Virus Program, Frederick, MD 21702 USA;

    Massachusetts Gen Hosp, Radon Inst MGH MIT & Harvard, Howard Hughes Med Inst, Cambridge, MA 02139 USA|Harvard Univ, Sch Med, Cambridge, MA 02139 USA;

    Celldex Therapeut Inc, Hampton, NJ 08827 USA;

    Cornell Univ, Div Infect Dis, Weill Med Coll, New York, NY 10065 USA;

    Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany|Partner Site Bonn Cologne, German Ctr Infect Res DZIF, Cologne, Germany;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA|Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA;

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