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

M Caskey, F Klein, JCC Lorenzi, MS Seaman… - Nature, 2015 - nature.com
M Caskey, F Klein, JCC Lorenzi, MS Seaman, AP West Jr, N Buckley, G Kremer, L Nogueira…
Nature, 2015nature.com
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,). 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 …
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 , ). 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.
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