@article{f63061f204af4673a327c4ec6f9d395e,
title = "Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117",
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 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.",
author = "Marina Caskey and Florian Klein and Lorenzi, {Julio C.C.} and Seaman, {Michael S.} and West, {Anthony P.} and Noreen Buckley and Gisela Kremer and Lilian Nogueira and Malte Braunschweig and Scheid, {Johannes F.} and Horwitz, {Joshua A.} and Irina Shimeliovich and Sivan Ben-Avraham and Maggi Witmer-Pack and Martin Platten and Clara Lehmann and Burke, {Leah A.} and Thomas Hawthorne and Gorelick, {Robert J.} and Walker, {Bruce D.} and Tibor Keler and Gulick, {Roy M.} and Gerd F{\"a}tkenheuer and Schlesinger, {Sarah J.} and Nussenzweig, {Michel C.}",
note = "Funding Information: Acknowledgements We thank all individuals who participated in this study. We thank the Rockefeller University Hospital Clinical Research Support Office and nursing staff, as well as T. K{\"u}mmerle, C. Wyen, and L. Siegel for help with recruitment; S. Kiss for ophthalmologic assessments; F. Maldarelli and J. Lifson for single-copy analysis and B. Freemire for technical assistance; J. Pring, A. Almaktari, C. Unsen, S. Hadrigan, E. Thomas, H. Gruell, D. Gillor, and U. Sandaradura de Silva for sample processing and study coordination, and N. Rodziewicz for help with HIV-1 culturing. We thank A. Louie and C. Conrad for help with regulatory submissions; L. Thomas for IND-enabling studies, L. Vitale for cell line and anti-idiotype antibody development, B. Riordan, A. Rayo and J. Andreozzi for anti-idiotype ELISA method development and sample analysis, R. Hammond for process development, and S. DiSciullo for 3BNC117 manufacturing; J. Perry for performing neutralization assays. We thank M. Suarez-Farinas for support with statistical analysis; P. Fast and H. Park for clinical monitoring; and E. Gotschlich and B. Coller for input on study design. J.C.C.L. is supported by an award from CNPq {\textquoteleft}{\textquoteleft}Ciencia sem Fronteiras{\textquoteright}{\textquoteright} Brazil (248676/2013-0). This work was supported in part by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) Grants OPP1033115 (M.C.N.), OPP1092074 (M.C.N.), OPP1040753 (A.P.W.) and OPP1032144 (M.S.S.), and U19AI111825-01 Cooperative Centers on Human Immunology from NIH to M.C.N., by grant #UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), by a grant from the Robertson Foundation to M.C.N., in part with Federal funds from the NCI/NIH, under Contract No. HHSN261200800001E, and a grant from the German Center for Infection Research (DZIF) to G.F. 3BNC117 was generated from a subject in the International HIV Controller Study, supported by the Mark and Lisa Schwartz Foundation and CAVD Grant 43307. M.C.N. and B.D.W. are Howard Hughes Medical Institute Investigators. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = apr,
day = "8",
doi = "10.1038/nature14411",
language = "English",
volume = "522",
pages = "487--491",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7557",
}
