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Fulfilling Paul Ehrlich’s Dream: therapeutics with activity on demand

Total Cost €


EC-Contrib. €






 ZAUBERKUGEL project word cloud

Explore the words cloud of the ZAUBERKUGEL project. It provides you a very rough idea of what is the project "ZAUBERKUGEL" about.

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Project "ZAUBERKUGEL" data sheet

The following table provides information about the project.


Organization address
address: Raemistrasse 101
postcode: 8092

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Project website
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

'Paul Ehrlich was the first scientist to postulate that if a compound could be made that selectively targeted disease-causing cells, then this agent could be used for the delivery of a toxin, which would enable a pharmacotherapy of unprecedented potency and selectivity. With this procedure, a 'magic bullet' (Zauberkugel, his term for an ideal therapeutic agent) would be created, that killed diseased cells while sparing normal tissues. The concept of a 'magic bullet' was to some extent realized by the invention of monoclonal antibodies, as these molecules provide a very specific binding affinity to their cognate target. However, monoclonal antibodies used as single agents are typically not able to induce cures for cancer or chronic inflammatory diseases. More recently, intense academic and industrial research activities have aimed at “arming” monoclonal antibodies with drugs or cytokines, in order to preferentially deliver these therapeutic payloads to the site of disease. Unfortunately, in most cases, 'armed' antibody products still cause unacceptable toxicities, which prevent escalation to potentially curative dose regimens. In this Project, I outline a therapeutic strategy, which relies on the use of extremely specific tumor targeting agents, for the selective delivery of payloads, which can be conditionally activated at the site of disease. Methodologies for the conditional generation of active payloads include the stepwise non-covalent assembly of cytokines and the controlled release of cytotoxic drugs at suitable time points after injection, when the concentration of therapeutic agent in normal organs is acceptably low. Response to therapy will be profiled using innovative proteomic methodologies, based on HLA-peptidome analysis. Pharmaceutical agents with “activity on demand” hold a considerable potential not only for the therapy of cancer, but also for the treatment of other serious diseases, including certain highly debilitating chronic inflammatory condition'


year authors and title journal last update
List of publications.
2020 Patrizia Murer, Louis Plüss, Dario Neri
A novel human monoclonal antibody specific to the A33 glycoprotein recognizes colorectal cancer and inhibits metastasis
published pages: 1714371, ISSN: 1942-0870, DOI: 10.1080/19420862.2020.1714371
mAbs 12/1 2020-04-24
2020 Jacqueline Mock, Christian Pellegrino, Dario Neri
A universal reporter cell line for bioactivity evaluation of engineered cytokine products
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-020-60182-4
Scientific Reports 10/1 2020-04-24
2019 Sheila Dakhel, Tiziano Ongaro, Baptiste Gouyou, Mattia Matasci, Alessandra Villa, Dario Neri, Samuele Cazzamalli
Targeted enhancement of the therapeutic window of L19-TNF by transient and selective inhibition of RIPK1-signaling cascade
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.27320
Oncotarget 10/62 2020-02-06
2019 Dario Neri
Antibody–Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity
published pages: 348-354, ISSN: 2326-6066, DOI: 10.1158/2326-6066.cir-18-0622
Cancer Immunology Research 7/3 2020-02-06
2019 Adrián Gironda-Martínez, Dario Neri, Florent Samain, Etienne J. Donckele
DNA-Compatible Diazo-Transfer Reaction in Aqueous Media Suitable for DNA-Encoded Chemical Library Synthesis
published pages: 9555-9558, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.9b03726
Organic Letters 21/23 2020-02-06
2019 Cornelia Hutmacher, Nicolás Gonzalo Núñez, Anna Rita Liuzzi, Burkhard Becher, Dario Neri
Targeted Delivery of IL2 to the Tumor Stroma Potentiates the Action of Immune Checkpoint Inhibitors by Preferential Activation of NK and CD8 + T Cells
published pages: 572-583, ISSN: 2326-6066, DOI: 10.1158/2326-6066.cir-18-0566
Cancer Immunology Research 7/4 2020-02-06
2019 Emanuele Puca, Philipp Probst, Marco Stringhini, Patrizia Murer, Giovanni Pellegrini, Samuele Cazzamalli, Cornelia Hutmacher, Baptiste Gouyou, Sarah Wulhfard, Mattia Matasci, Alessandra Villa, Dario Neri
The antibody‐based delivery of interleukin‐12 to solid tumors boosts NK and CD8 + T cell activity and synergizes with immune checkpoint inhibitors
published pages: , ISSN: 0020-7136, DOI: 10.1002/ijc.32603
International Journal of Cancer 2020-02-06
2019 Emanuele Puca, Roberto De Luca, Frauke Seehusen, Josep Maria Monné Rodriguez, Dario Neri
Comparative evaluation of bolus and fractionated administration modalities for two antibody-cytokine fusions in immunocompetent tumor-bearing mice
published pages: , ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2019.11.036
Journal of Controlled Release 2020-02-06
2019 Padma Akkapeddi, Rita Fragoso, Julie A. Hixon, Ana Sofia Ramalho, Mariana L. Oliveira, Tânia Carvalho, Andreas Gloger, Mattia Matasci, Francisco Corzana, Scott K. Durum, Dario Neri, Gonçalo J. L. Bernardes, João T. Barata
A fully human anti-IL-7Rα antibody promotes antitumor activity against T-cell acute lymphoblastic leukemia
published pages: 2155-2168, ISSN: 0887-6924, DOI: 10.1038/s41375-019-0434-8
Leukemia 33/9 2020-02-06
2018 Roberto De Luca, Dario Neri
Potentiation of PD-L1 blockade with a potency-matched dual cytokine–antibody fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains
published pages: 1381-1391, ISSN: 0340-7004, DOI: 10.1007/s00262-018-2194-0
Cancer Immunology, Immunotherapy 67/9 2020-02-04
2019 Anja Sophie Schmid, Dario Neri
Design and characterisation of a novel interleukin-15 receptor alpha fusion protein and analysis of interleukin-15 complexation
published pages: e0219313, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0219313
PLOS ONE 14/7 2020-02-04
2018 Cazzamalli, Samuele; Figueras, Eduard; Pethő, Lilla; Borbély, Adina; Steinkühler, Christian; Neri, Dario; Sewald, Norbert
In Vivo Antitumor Activity of a Novel Acetazolamide–Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas
published pages: 14726-14731, ISSN: 2470-1343, DOI: 10.3929/ethz-b-000304161
ACS Omega, 3 (11) 1 2020-02-04
2018 Simon Schwager, Silvana Renner, Teresa Hemmerle, Sinem Karaman, Steven T. Proulx, Roman Fetz, Alexandra Michaela Golding-Ochsenbein, Philipp Probst, Cornelia Halin, Dario Neri, Michael Detmar
Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation
published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.124850
JCI Insight 3/23 2020-01-30
2019 Barbara Ziffels, Marco Stringhini, Philipp Probst, Tim Fugmann, Theo Sturm, Dario Neri
Antibody-Based Delivery of Cytokine Payloads to Carbonic Anhydrase IX Leads to Cancer Cures in Immunocompetent Tumor-Bearing Mice
published pages: 1544-1554, ISSN: 1535-7163, DOI: 10.1158/1535-7163.mct-18-1301
Molecular Cancer Therapeutics 18/9 2020-01-30
2019 Patrizia Murer, Dario Neri
Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation
published pages: 42-53, ISSN: 1871-6784, DOI: 10.1016/j.nbt.2019.04.002
New Biotechnology 52 2020-01-30
2019 Patrizia Murer, Jonathan D. Kiefer, Louis Plüss, Mattia Matasci, Sandra L. Blümich, Marco Stringhini, Dario Neri
Targeted Delivery of TNF Potentiates the Antibody-Dependent Cell-Mediated Cytotoxicity of an Anti-Melanoma Immunoglobulin
published pages: 1339-1348, ISSN: 0022-202X, DOI: 10.1016/j.jid.2018.11.028
Journal of Investigative Dermatology 139/6 2020-01-30
2019 Barbara Ziffels, Anna Grötsch, Lubna Al-Bayati, Dario Neri
Targeted delivery of calreticulin to ED-A fibronectin leads to tumor-growth retardation
published pages: 53-58, ISSN: 0168-1656, DOI: 10.1016/j.jbiotec.2018.12.007
Journal of Biotechnology 290 2020-01-30
2019 Cornelia Hutmacher, Dario Neri
Antibody-cytokine fusion proteins: Biopharmaceuticals with immunomodulatory properties for cancer therapy
published pages: 67-91, ISSN: 0169-409X, DOI: 10.1016/j.addr.2018.09.002
Advanced Drug Delivery Reviews 141 2020-01-30
2019 Roberto De Luca, Baptiste Gouyou, Tiziano Ongaro, Alessandra Villa, Barbara Ziffels, Alessandro Sannino, Gianluca Buttinoni, Simone Galeazzi, Mirko Mazzacuva, Dario Neri
A Novel Fully-Human Potency-Matched Dual Cytokine-Antibody Fusion Protein Targets Carbonic Anhydrase IX in Renal Cell Carcinomas
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2019.01228
Frontiers in Oncology 9 2020-01-30
2019 Cornelia Hutmacher, Laura Volta, Francesco Rinaldi, Patrizia Murer, Renier Myburgh, Markus G. Manz, Dario Neri
Development of a novel fully-human anti-CD123 antibody to target acute myeloid leukemia
published pages: 106178, ISSN: 0145-2126, DOI: 10.1016/j.leukres.2019.106178
Leukemia Research 84 2020-01-30
2018 Roberto De Luca, Paul Kachel, Klara Kropivsek, Berend Snijder, Markus G Manz, Dario Neri
A novel dual-cytokine–antibody fusion protein for the treatment of CD38-positive malignancies
published pages: 173-179, ISSN: 1741-0126, DOI: 10.1093/protein/gzy015
Protein Engineering, Design and Selection 31/5 2020-01-30
2019 Alessandro Sannino, Elena Gabriele, Martina Bigatti, Sara Mulatto, Jacopo Piazzi, Jörg Scheuermann, Dario Neri, Etienne J. Donckele, Florent Samain
Quantitative Assessment of Affinity Selection Performance by Using DNA‐Encoded Chemical Libraries
published pages: 955-962, ISSN: 1439-4227, DOI: 10.1002/cbic.201800766
ChemBioChem 20/7 2020-01-30
2019 Philipp Probst, Marco Stringhini, Danilo Ritz, Tim Fugmann, Dario Neri
Antibody-based Delivery of TNF to the Tumor Neovasculature Potentiates the Therapeutic Activity of a Peptide Anticancer Vaccine
published pages: 698-709, ISSN: 1078-0432, DOI: 10.1158/1078-0432.CCR-18-1728
Clinical Cancer Research 25/2 2020-01-30
2017 Gunther Zimmermann, Yizhou Li, Ulrike Rieder, Martin Mattarella, Dario Neri, Jörg Scheuermann
Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries
published pages: , ISSN: 1439-4227, DOI: 10.1002/cbic.201600637
ChemBioChem 2019-07-05
2016 Andreas Gloger, Danilo Ritz, Tim Fugmann, Dario Neri
Mass spectrometric analysis of the HLA class I peptidome of melanoma cell lines as a promising tool for the identification of putative tumor-associated HLA epitopes
published pages: 1377-1393, ISSN: 0340-7004, DOI: 10.1007/s00262-016-1897-3
Cancer Immunology, Immunotherapy 65/11 2019-07-05
2018 Samuele Cazzamalli, Barbara Ziffels, Fontaine Widmayer, Patrizia Murer, Giovanni Pellegrini, Francesca Pretto, Sarah Wulhfard, Dario Neri
Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2
published pages: 3656-3667, ISSN: 1078-0432, DOI: 10.1158/1078-0432.CCR-17-3457
Clinical Cancer Research 24/15 2019-07-05
2017 Yizhou Li, Gunther Zimmermann, Jörg Scheuermann, Dario Neri
Quantitative PCR is a Valuable Tool to Monitor the Performance of DNA-Encoded Chemical Library Selections
published pages: , ISSN: 1439-4227, DOI: 10.1002/cbic.201600626
ChemBioChem 2019-07-05
2016 Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to Renal Cell Carcinoma
published pages: 2926-2935, ISSN: 1535-7163, DOI: 10.1158/1535-7163.MCT-16-0283
Molecular Cancer Therapeutics 15/12 2019-07-05
2017 Tim Fugmann, Adriana Sofron, Danilo Ritz, Franziska Bootz, Dario Neri
The MHC Class II Immunopeptidome of Lymph Nodes in Health and in Chemically Induced Colitis
published pages: 1357-1364, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1601157
The Journal of Immunology 198/3 2019-07-05
2018 Yizhou Li, Roberto De Luca, Samuele Cazzamalli, Francesca Pretto, Davor Bajic, Jörg Scheuermann, Dario Neri
Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold
published pages: 441-448, ISSN: 1755-4330, DOI: 10.1038/s41557-018-0017-8
Nature Chemistry 10/4 2019-07-05
2016 Danilo Ritz, Andreas Gloger, Benjamin Weide, Claus Garbe, Dario Neri, Tim Fugmann
High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients’ sera
published pages: n/a-n/a, ISSN: 1615-9853, DOI: 10.1002/pmic.201500445
PROTEOMICS 2019-07-05
2018 Danilo Ritz, Emiliano Sani, Hanna Debiec, Pierre Ronco, Dario Neri, Tim Fugmann
Membranal and blood-soluble HLA class II peptidome analyses using data-dependent and independent acquisition
published pages: , ISSN: 1615-9853, DOI: 10.1002/pmic.201700246
PROTEOMICS 2019-07-05
2018 Nicholas Favalli, Stefan Biendl, Marco Hartmann, Jacopo Piazzi, Filippo Sladojevich, Susanne Gräslund, Peter J. Brown, Katja Näreoja, Herwig Schüler, Jörg Scheuermann, Raphael Franzini, Dario Neri
A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition
published pages: 1303-1307, ISSN: 1860-7179, DOI: 10.1002/cmdc.201800193
ChemMedChem 13/13 2019-07-05
2017 Alberto Dal Corso, Samuele Cazzamalli, Rémy Gébleux, Martin Mattarella, Dario Neri
Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody–Drug Conjugates
published pages: 1826-1833, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.7b00304
Bioconjugate Chemistry 28/7 2019-07-05
2017 Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma
published pages: 39-45, ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2016.11.023
Journal of Controlled Release 246 2019-07-05
2018 Barbara Ziffels, Francesca Pretto, Dario Neri
Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer without establishing protective immunity
published pages: 177-188, ISSN: 1750-743X, DOI: 10.2217/imt-2017-0119
Immunotherapy 10/3 2019-07-05
2018 Anja Sophie Schmid, Teresa Hemmerle, Francesca Pretto, Anja Kipar, Dario Neri
Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone for the reduction of inflammation in arthritis
published pages: , ISSN: 1462-0324, DOI: 10.1093/rheumatology/kex447
Rheumatology 2019-07-05
2016 Yizhou Li, Elena Gabriele, Florent Samain, Nicholas Favalli, Filippo Sladojevich, Jörg Scheuermann, Dario Neri
Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries
published pages: 438-443, ISSN: 2156-8952, DOI: 10.1021/acscombsci.6b00058
ACS Combinatorial Science 18/8 2019-07-05
2017 Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Targeted Delivery of Cytotoxic Drugs: Challenges, Opportunities and New Developments
published pages: 712-715, ISSN: 0009-4293, DOI: 10.2533/chimia.2017.712
CHIMIA International Journal for Chemistry 71/10 2019-07-05
2017 Benjamin Weide, Dario Neri, Giuliano Elia
Intralesional treatment of metastatic melanoma: a review of therapeutic options
published pages: , ISSN: 0340-7004, DOI: 10.1007/s00262-016-1952-0
Cancer Immunology, Immunotherapy 2019-07-05
2018 De Luca R, Kachel P, Kropivsek K, Snijder B, Manz MG, Neri D
OUP accepted manuscript
published pages: , ISSN: 1741-0126, DOI: 10.1093/protein/gzy015
Protein Engineering, Design, and Selection 2019-07-05
2018 Dario Neri, Richard A. Lerner
DNA-Encoded Chemical Libraries: A Selection System Based On Endowing Organic Compounds with Amplifiable Information
published pages: , ISSN: 0066-4154, DOI: 10.1146/annurev-biochem-062917-012550
Annual Review of Biochemistry 87/1 2019-07-05
2016 Dario Venetz, Danil Koovely, Bruce Weder, Dario Neri
Targeted Reconstitution of Cytokine Activity upon Antigen Binding using Split Cytokine Antibody Fusion Proteins
published pages: 18139-18147, ISSN: 0021-9258, DOI: 10.1074/jbc.M116.737734
Journal of Biological Chemistry 291/35 2019-07-05
2017 Alberto Dal Corso, Rémy Gébleux, Patrizia Murer, Alex Soltermann, Dario Neri
A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo
published pages: 211-218, ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2017.08.040
Journal of Controlled Release 264 2019-07-05
2016 F. Bootz, D. Venetz, B. Ziffels, D. Neri
Different tissue distribution properties for glycosylation variants of fusion proteins containing the p40 subunit of murine interleukin-12
published pages: 445-455, ISSN: 1741-0126, DOI: 10.1093/protein/gzw038
Protein Engineering Design and Selection 29/10 2019-07-05
2017 Danilo Ritz, Andreas Gloger, Dario Neri, Tim Fugmann
Purification of soluble HLA class I complexes from human serum or plasma deliver high quality immuno peptidomes required for biomarker discovery
published pages: 1600364, ISSN: 1615-9853, DOI: 10.1002/pmic.201600364
PROTEOMICS 17/1-2 2019-07-05
2016 Jonathan D. Kiefer, Dario Neri
Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site
published pages: 178-192, ISSN: 0105-2896, DOI: 10.1111/imr.12391
Immunological Reviews 270/1 2019-07-05
2017 Philipp Probst, Janine Kopp, Annette Oxenius, Mario P. Colombo, Danilo Ritz, Tim Fugmann, Dario Neri
Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8 + T-cell Recognition of a Retroviral Antigen
published pages: 3644-3654, ISSN: 0008-5472, DOI: 10.1158/0008-5472.CAN-16-2946
Cancer Research 77/13 2019-07-05
2015 R. Gebleux, S. Wulhfard, G. Casi, D. Neri
Antibody Format and Drug Release Rate Determine the Therapeutic Activity of Noninternalizing Antibody-Drug Conjugates
published pages: 2606-2612, ISSN: 1535-7163, DOI: 10.1158/1535-7163.MCT-15-0480
Molecular Cancer Therapeutics 14/11 2019-07-05
2017 Gunther Zimmermann, Ulrike Rieder, Davor Bajic, Sara Vanetti, Apirat Chaikuad, Stefan Knapp, Jörg Scheuermann, Martin Mattarella, Dario Neri
A Specific and Covalent JNK-1 Ligand Selected from an Encoded Self-Assembling Chemical Library
published pages: 8152-8155, ISSN: 0947-6539, DOI: 10.1002/chem.201701644
Chemistry - A European Journal 23/34 2019-07-05
2018 Samuele Cazzamalli, Alberto Dal Corso, Fontaine Widmayer, Dario Neri
Chemically Defined Antibody– and Small Molecule–Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis
published pages: 1617-1621, ISSN: 0002-7863, DOI: 10.1021/jacs.7b13361
Journal of the American Chemical Society 140/5 2019-07-05
2018 Nicholas Favalli, Gabriele Bassi, Jörg Scheuermann, Dario Neri
DNA-encoded chemical libraries - achievements and remaining challenges
published pages: 2168-2180, ISSN: 0014-5793, DOI: 10.1002/1873-3468.13068
FEBS Letters 592/12 2019-07-05
2016 Franziska Bootz, Dario Neri
Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions
published pages: 180-189, ISSN: 1359-6446, DOI: 10.1016/j.drudis.2015.10.012
Drug Discovery Today 21/1 2019-07-05
2017 Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
Potency-matched Dual Cytokine–Antibody Fusion Proteins for Cancer Therapy
published pages: 2442-2451, ISSN: 1535-7163, DOI: 10.1158/1535-7163.MCT-17-0211
Molecular Cancer Therapeutics 16/11 2019-07-05
2017 Rémy Gébleux, Marco Stringhini, Ruben Casanova, Alex Soltermann, Dario Neri
Non-internalizing antibody-drug conjugates display potent anti-cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix
published pages: 1670-1679, ISSN: 0020-7136, DOI: 10.1002/ijc.30569
International Journal of Cancer 140/7 2019-07-05
2017 Danilo Ritz, Jonny Kinzi, Dario Neri, Tim Fugmann
Data-Independent Acquisition of HLA Class I Peptidomes on the Q Exactive Mass Spectrometer Platform
published pages: 1700177, ISSN: 1615-9853, DOI: 10.1002/pmic.201700177
PROTEOMICS 17/19 2019-07-05

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