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Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation

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Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. / Danquah, Welbeck; Meyer-Schwesinger, Catherine; Rissiek, Björn; Pinto, Carolina ; Serracant-Prat, Arnau; Amadi, Miriam ; Iacenda, Domenica ; Knop, Jan-Hendrik; Hammel, Anna; Bergmann, Philine ; Schwarz, Nicole; Assunção, Joana; Rotthier, Wendy; Haag, Friedrich; Tolosa, Eva; Bannas, Peter; Boué-Grabot, Eric; Magnus, Tim; Laeremans, Toon; Stortelers, Catelijne; Nolte, Friedrich.

in: SCI TRANSL MED, Jahrgang 8, Nr. 366, 23.11.2016, S. 366ra162.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Danquah, W, Meyer-Schwesinger, C, Rissiek, B, Pinto, C, Serracant-Prat, A, Amadi, M, Iacenda, D, Knop, J-H, Hammel, A, Bergmann, P, Schwarz, N, Assunção, J, Rotthier, W, Haag, F, Tolosa, E, Bannas, P, Boué-Grabot, E, Magnus, T, Laeremans, T, Stortelers, C & Nolte, F 2016, 'Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation', SCI TRANSL MED, Jg. 8, Nr. 366, S. 366ra162. https://doi.org/10.1126/scitranslmed.aaf8463

APA

Danquah, W., Meyer-Schwesinger, C., Rissiek, B., Pinto, C., Serracant-Prat, A., Amadi, M., Iacenda, D., Knop, J-H., Hammel, A., Bergmann, P., Schwarz, N., Assunção, J., Rotthier, W., Haag, F., Tolosa, E., Bannas, P., Boué-Grabot, E., Magnus, T., Laeremans, T., ... Nolte, F. (2016). Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. SCI TRANSL MED, 8(366), 366ra162. https://doi.org/10.1126/scitranslmed.aaf8463

Vancouver

Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M et al. Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. SCI TRANSL MED. 2016 Nov 23;8(366):366ra162. https://doi.org/10.1126/scitranslmed.aaf8463

Bibtex

@article{82031d7f2143430c958147a3af1e7b6a,
title = "Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation",
abstract = "Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β). To further explore its function, we generated and characterized nanobodies against mouse P2X7 that effectively blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and ameliorated experimental glomerulonephritis and allergic contact dermatitis. We also generated nanobody Dano1, which specifically inhibited human P2X7. In endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL-1β release than small-molecule P2X7 antagonists currently in clinical development. Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7.POM-Newsletter",
author = "Welbeck Danquah and Catherine Meyer-Schwesinger and Bj{\"o}rn Rissiek and Carolina Pinto and Arnau Serracant-Prat and Miriam Amadi and Domenica Iacenda and Jan-Hendrik Knop and Anna Hammel and Philine Bergmann and Nicole Schwarz and Joana Assun{\c c}{\~a}o and Wendy Rotthier and Friedrich Haag and Eva Tolosa and Peter Bannas and Eric Bou{\'e}-Grabot and Tim Magnus and Toon Laeremans and Catelijne Stortelers and Friedrich Nolte",
note = "Copyright {\textcopyright} 2016, American Association for the Advancement of Science.",
year = "2016",
month = nov,
day = "23",
doi = "10.1126/scitranslmed.aaf8463",
language = "English",
volume = "8",
pages = "366ra162",
journal = "SCI TRANSL MED",
issn = "1946-6234",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "366",

}

RIS

TY - JOUR

T1 - Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation

AU - Danquah, Welbeck

AU - Meyer-Schwesinger, Catherine

AU - Rissiek, Björn

AU - Pinto, Carolina

AU - Serracant-Prat, Arnau

AU - Amadi, Miriam

AU - Iacenda, Domenica

AU - Knop, Jan-Hendrik

AU - Hammel, Anna

AU - Bergmann, Philine

AU - Schwarz, Nicole

AU - Assunção, Joana

AU - Rotthier, Wendy

AU - Haag, Friedrich

AU - Tolosa, Eva

AU - Bannas, Peter

AU - Boué-Grabot, Eric

AU - Magnus, Tim

AU - Laeremans, Toon

AU - Stortelers, Catelijne

AU - Nolte, Friedrich

N1 - Copyright © 2016, American Association for the Advancement of Science.

PY - 2016/11/23

Y1 - 2016/11/23

N2 - Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β). To further explore its function, we generated and characterized nanobodies against mouse P2X7 that effectively blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and ameliorated experimental glomerulonephritis and allergic contact dermatitis. We also generated nanobody Dano1, which specifically inhibited human P2X7. In endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL-1β release than small-molecule P2X7 antagonists currently in clinical development. Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7.POM-Newsletter

AB - Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β). To further explore its function, we generated and characterized nanobodies against mouse P2X7 that effectively blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and ameliorated experimental glomerulonephritis and allergic contact dermatitis. We also generated nanobody Dano1, which specifically inhibited human P2X7. In endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL-1β release than small-molecule P2X7 antagonists currently in clinical development. Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7.POM-Newsletter

U2 - 10.1126/scitranslmed.aaf8463

DO - 10.1126/scitranslmed.aaf8463

M3 - SCORING: Journal article

C2 - 27881823

VL - 8

SP - 366ra162

JO - SCI TRANSL MED

JF - SCI TRANSL MED

SN - 1946-6234

IS - 366

ER -