Dario Neri

ETH Zurich, Zürich, Zurich, Switzerland

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Publications (339)1953.06 Total impact

  • Franziska Bootz · Dario Neri ·
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    ABSTRACT: Antibody-cytokine fusion proteins, often referred to as immunocytokines, represent a novel class of biopharmaceutical agents that combine the disease-homing activity of certain antibodies with the immunomodulatory properties of cytokine payloads. Originally, immunocytokines were mainly developed for cancer therapy applications. More recently, however, the use of anti-inflammatory cytokines for the treatment of chronic inflammatory conditions and to treat autoimmune diseases has been considered. This review analyzes basic principles in the design of immunocytokines and describes the most advanced products in preclinical and clinical development.
    Drug discovery today 11/2015; DOI:10.1016/j.drudis.2015.10.012 · 6.69 Impact Factor
  • Adriana Sofron · Danilo Ritz · Dario Neri · Tim Fugmann ·
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    ABSTRACT: The reliable identification of peptides bound to MHC class II is fundamental for the study of the host immune response against pathogens and the pathogenesis of autoimmune conditions. Here we describe an improved methodology combining immuno-affinity enrichment of MHC class II complexes, optimized elution conditions and quadrupole Orbitrap mass spectrometry-based characterization of the immunopeptidome. The methodology allowed the identification of over 1000 peptides with 1% false discovery rate from 10(8) murine A20 lymphoma cells. The study revealed the I-A(d) specific motif in high resolution after multi-sequence alignment. The methodology was generally applied to the purification of MHC class II from cell lines and murine spleens. We identified 2963 peptides from BALB/c and 2712 from C57BL/6 mouse spleens. The identification of peptides that bound to MHC class II in vitro and in vivo will facilitate the characterization of T-cell specificities, as well as the development of biotherapeutics and vaccines. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 10/2015; DOI:10.1002/eji.201545930 · 4.03 Impact Factor
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    ABSTRACT: Management of chronic rejection is challenging since there are not sufficient preventive or therapeutic strategies. The rejection process leads to overexpression of ED-A(+) fibronectin (ED-A(+) Fn). The human antibody F8, specific to ED-A(+) Fn, may serve as a vehicle for targeted delivery of bioactive payloads, e.g. interleukin 10 (IL-10). The aim of this study was to investigate the therapeutic effects of the fusion protein F8-interleukin-10 (F8-IL10) in the process of chronic rejection development. A heterotopic rat heart transplantation model was used to induce chronic rejection. For therapeutic interventions, the immunocytokines F8-humanIL10 (DEKAVIL), F8-ratIL10 as well as KSF-humanIL10 (irrelevant antigen-specificity) were used. Treatment was performed weekly for 10weeks starting at day 7 after transplantation (1mg/animal). In the cardiac allografts, treatment with F8-huIL10 or F8-ratIL10 was associated with increased heart weights, a higher grade of chronic rejection, increased CIF, higher protein expression levels of alpha-smooth muscle actin (α-SMA), an augmented infiltration with inflammatory cells (CD4+, CD8+ and CD68+ cells) and higher serum levels of brain natriuretic peptide (BNP) compared to the control groups. All observed treatment effects are transplantation-specific since the F8 antibody is specific to ED-A(+) Fn that is not expressed in healthy hearts. A clear targeting effect of F8-huIL10 as well as F8-ratIL10 could be proven. Against that background, a further study is needed to address the question, if F8-IL10 treatment is capable to reduce CAV and CIF starting at a time point when chronic rejection has fully developed (therapeutic approach). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 09/2015; 195. DOI:10.1016/j.ijcard.2015.05.144 · 4.04 Impact Factor
  • Rémy Gébleux · Sarah Wulhfard · Giulio Casi · Dario Neri ·
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    ABSTRACT: The development of antibody-drug conjugates (ADCs), a promising class of anti-cancer agents, has traditionally relied on the use of antibodies capable of selective internalization in tumor cells. We have recently shown that also non-internalizing antibodies, coupled to cytotoxic drugs by means of disulfide linkers that can be cleaved in the tumor extracellular environment, can display a potent therapeutic activity. Here, we have compared the tumor targeting properties, drug release rates and therapeutic performance of two antibody-drug conjugates, based on the maytansinoid DM1 thiol drug and on the F8 antibody, directed against the alternatively-spliced EDA domain of fibronectin. The antibody was used in IgG or in small immune protein (SIP) format. In both cases, DM1 was coupled to unpaired cysteine residues, resulting in a drug-antibody ratio of 2. In biodistribution studies, SIP(F8)-SS-DM1 accumulated in the tumor and cleared from circulation more rapidly than IgG(F8)-SS-DM1. However, the ADC based on the IgG format exhibited a higher tumor uptake at later time points (e.g., 33 %IA/g against 8 %IA/g at 24 h after intravenous administration). In mouse plasma, surprisingly, the ADC products in IgG format were substantially more stable compared to the SIP format (half-lives > 48 h and < 3 h at 37 ºC, respectively), revealing a novel mechanism for the control of disulfide-based drug release rates. Therapy experiments in immunocompetent mice bearing murine F9 tumors revealed that SIP(F8)-SS-DM1 was more efficacious than IgG(F8)-SS-DM1 when the two products were compared either in an equimolar basis or at equal milligram doses. Copyright © 2015, American Association for Cancer Research.
    Molecular Cancer Therapeutics 08/2015; DOI:10.1158/1535-7163.MCT-15-0480 · 5.68 Impact Factor
  • Jörg Scheuermann · Dario Neri ·
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    ABSTRACT: DNA-encoded chemical libraries consist of a set of organic molecules, which are individually coupled to a DNA fragment. These allow synthesis and screening of collections of chemical compounds of unprecedented size and diversity. This chapter reviews the main concepts and applications related to Dual-pharmacophore DNA-encoded chemical libraries. It characterizes the magnitude of the chelate effect in DNA-encoded dual-pharmacophore structures, using short DNA fragments in heteroduplex format to scaffold pairs of binding molecules with defined spatial arrangements revealing apparent improvement of ≥1000-fold for the bidentate binding mode compared to monodentate binding. Dual-pharmacophore chemical libraries can be constructed by the combinatorial self-assembly of two complementary sublibraries, in which each DNA strand displays a small molecule. Dual-pharmacophore DNA-encoded chemical libraries represent a nice complement to conventional fragment-based lead discovery strategies, and the next few years will reveal the real potential of this technology for the generation of pharmaceutically useful products.
    Current Opinion in Chemical Biology 06/2015; 26. DOI:10.1016/j.cbpa.2015.02.021 · 6.81 Impact Factor
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    ABSTRACT: Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses. In syngeneic F9 tumour bearing 129/FvHsd mice tumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry. Tumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression. An additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    Radiotherapy and Oncology 06/2015; 183(3). DOI:10.1016/j.radonc.2015.06.019 · 4.36 Impact Factor
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    ABSTRACT: The potential of DNA-encoded combinatorial libraries (DECLs) as tools for hit discovery crucially relies on the availability of methods for their synthesis at acceptable purity and quality. Incomplete reactions in the presence of DNA can noticeably affect the purity of DECLs and methods to selectively remove unreacted oligonucleotide-based starting products would likely enhance the quality of DECL screening results. We describe an approach to selectively remove unreacted oligonucleotide starting products from reaction mixtures and demonstrate its applicability in the context of acylation of amino-modified DNA. Following an amide bond forming reaction, we treat unreacted amino-modified DNAs with biotinylating reagents and isolate the corresponding biotinylated oligonucleotides from the reaction mixture by affinity capture on streptavidin-coated sepharose. This approach, which yields the desired DNA-conjugate at enhanced purity, can be applied both to reactions performed in solution and to procedures in which DNA is immobilized on an anion exchange solid support.
    06/2015; 17(7). DOI:10.1021/acscombsci.5b00072
  • Giulio Casi · Dario Neri ·
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    ABSTRACT: Conventional cancer chemotherapy heavily relies on the use of cytotoxic agents, which typically do not preferentially localize at the tumor site and cause toxicity to normal organs, preventing dose escalation to therapeutically active regimens. In principle, antibodies and other ligands could be used for the selective pharmacodelivery of cytotoxic agents to the neoplastic mass. For many years, the availability of ligands, capable of selective internalization into tumor cells, has been considered to be an essential requirement for the development of targeted cytotoxics. This assumption, however, has recently been challenged on the basis of therapeutic data obtained with non-internalizing drug conjugates. Moreover, quantitative evaluations of the tumor targeting properties of antibodies and of small organic ligands have provided new insights for the implementation of optimal strategies for the development of targeted cytotoxics. In this article, we highlight opportunities and challenges associated with the clinical and industrial development of antibody-drug conjugates and small molecule-drug conjugates for cancer therapy.
    Journal of Medicinal Chemistry 06/2015; DOI:10.1021/acs.jmedchem.5b00457 · 5.45 Impact Factor
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    ABSTRACT: We describe the synthesis and screening of a DNA-encoded chemical library containing 76230 compounds. In this library, sets of amines and carboxylic acids are directly linked producing encoded compounds with compact structures and drug-like properties. Affinity screening of this library yielded inhibitors of the potential pharmaceutical target tankyrase 1, a poly(ADP-ribose) polymerase. These compounds have drug-like characteristics, and the most potent hit compound (X066/Y469) inhibited tankyrase 1 with an IC50 value of 250 nM.
    Journal of Medicinal Chemistry 06/2015; 58(12). DOI:10.1021/acs.jmedchem.5b00432 · 5.45 Impact Factor
  • Emil Bujak · Danilo Ritz · Dario Neri ·

    06/2015; 4(2):71-87. DOI:10.3390/antib4020071
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    ABSTRACT: Background F8-IL10 (Dekavil) is a fully human immunocytokine, composed of the antibody fragment F8, specific to the extradomain A of fibronectin (EDA-FN), fused to the anti-inflammatory cytokine interleukin-10 (IL-10) [1, 2]. F8-IL10 is currently being investigated as a new therapeutic strategy targeting the inflamed tissues in rheumatoid arthritis (RA). Objectives To determine the safety and tolerability of Dekavil when administered in combination with methotrexate (MTX) to patients suffering from RA who had failed at least one anti-TNFα drug therapy. To give a preliminary evaluation of the efficacy of Dekavil when administered in combination with MTX. Methods A Phase Ib non-placebo controlled clinical trial is currently ongoing in order to establish the maximum tolerated dose (MTD) of Dekavil when administered in combination with MTX. Cohorts of 3-6 patients are treated with escalating doses of Dekavil (6, 15, 30, 60, 110, 160, 210, 300, 450 and 600 μg/kg) in combination with a fixed dose of MTX. Dekavil is administered by subcutaneous injection once a week for a maximum of 8 weeks. Results As of today, the first eight cohorts of the study have been completed (dose levels from 6 to 300 μg/kg). Twenty-six patients are evaluable for safety. No dose limiting toxicities nor serious adverse events have been recorded. No MTD has yet been reached; the dose level of 450 μg/kg is currently ongoing. Mild injection site reaction has been reported in 54% of patients. Regarding systemic adverse reactions, one case of progressive anemia was reported in one patient treated at 160 μg/kg. All adverse reactions resolved after the end of treatment with minor or no therapeutic interventions. A therapeutic benefit of Dekavil, in terms of ACR response, has been recorded in the treated patients, even in subjects treated with low drug dosages. To date, 25 patients are evaluable for efficacy. Among this population, ACR20, 50 and 70 responses were achieved by 60%, 32% and 16% of patients, respectively. In addition, two patients treated at 30 μg/kg and 60 μg/kg dose levels achieved a long-lasting remission. Conclusions The promising safety profile, together with the preliminary efficacy responses in this non-placebo controlled trial led to the start of a Phase II placebo-controlled trial within the same patient population to verify the efficacy of low dosages of Dekavil in combination with MTX. The currently available data suggest the targeted delivery of IL-10 to the sites of inflammation is a promising therapeutic approach for RA. References Disclosure of Interest M. Galeazzi: None declared, G. Sebastiani: None declared, L. Bazzichi: None declared, E. Garcia Gonzalez Consultant for: Philogen, N. Ravenni Employee of: Philogen, L. Giovannoni Employee of: Philogen, J. Wilton Consultant for: Philogen, E. Selvi: None declared, M. Bardelli: None declared, C. Baldi: None declared, A. Iuliano: None declared, G. Minisola: None declared, R. Caporali: None declared, S. Bombardieri: None declared, D. Neri Shareholder of: Philogen
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):726.2-727. DOI:10.1136/annrheumdis-2015-eular.3889 · 10.38 Impact Factor
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    ABSTRACT: The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B-containing plaques has not been explored. This study evaluated whether [99mTc]-conjugated AP39 ([99mTc]-AP39), a single-chain antibody specific to ED-B, can be used for in vivo detection of atherosclerotic plaques in Western diet (WD)-fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT) control mice. Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were studied 4 hours after injecting [99mTc]-AP39 (148 MBq). Subsequently, mice were sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using histology, immuno-histochemistry, autoradiography, and morphometry. In vivo [99mTc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant signal activity in the plaque-ridden thoracic aorta (52.236±40.646 cpm/cm3) that co-localized with the aortic arch and the supra-aortic arteries in MRI scans. Low signal activity (9.468±4.976 cpm/cm3) was observed in WT mice. In apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/- mice confirmed the in vivo observation by demonstrating signal localization in atherosclerotic plaques. The size of autoradiography-positive plaque areas correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or macrophage-infiltrated (r=0.84, P<0.002) plaques. A significant correlation was found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas (r=0.93, P<0.01). [99mTc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.. 06/2015; 59(2):228-37. · 2.03 Impact Factor
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    Dario Neri ·

    Journal of Nuclear Medicine 05/2015; 56(8). DOI:10.2967/jnumed.115.159533 · 6.16 Impact Factor
  • Emil Bujak · Francesca Pretto · Dario Neri ·
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    ABSTRACT: Phosphatidylserine (PS) and other anionic phospholipids, which become exposed on the surface of proliferating endothelial cells, tumor cells and certain leukocytes, have been used as targets for the development of clinical-stage biopharmaceuticals. One of these products (bavituximab) is currently being investigated in Phase 3 clinical trials. There are conflicting reports on the ability of bavituximab and other antibodies to recognize PS directly or through beta-2 glycoprotein 1, a serum protein that is not highly conserved across species. Here, we report on the generation and characterization of two fully human antibodies directed against phosphatidylserine. One of these antibodies (PS72) bound specifically to phosphatidylserine and to phosphatidic acid, but did not recognize other closely related phospholipids, while the other antibody (PS41) also bound to cardiolipin. Both PS72 and PS41 stained 8/9 experimental tumor models in vitro, but both antibodies failed to exhibit a preferential tumor accumulation in vivo, as revealed by quantitative biodistribution analysis. Our findings indicate that anionic phospholipids are exposed and accessible in most tumor types, but cast doubts about the possibility of efficiently targeting tumors in vivo with PS-specific reagents.
    Investigational New Drugs 05/2015; 33(4). DOI:10.1007/s10637-015-0248-0 · 2.92 Impact Factor
  • Franziska Bootz · Anja Sophie Schmid · Dario Neri ·
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    ABSTRACT: The antibody-based pharmacodelivery of cytokines to sites of disease has been extensively studied for various indications but not for the treatment of inflammatory bowel diseases. Here, we report that the alternatively spliced EDA domain of fibronectin, a marker of angiogenesis and of tissue remodeling, is expressed in the dextran sodium sulfate mouse model of colitis and in patients with inflammatory bowel conditions, while being virtually undetectable in most normal adult tissues. Radiolabeled preparations of the F8 antibody, specific to the EDA domain of fibronectin, were shown to selectively localize to sites of inflammation in mice with colitis, as revealed by autoradiographic analysis. Fusion proteins of the F8 antibody with various murine payloads (interleukin-4, the p40 subunit of interleukin-12, interleukin-13) were administered to mice with colitis. IL12p40-F8 mediated an anti-inflammatory activity, which was comparable with the one of cyclosporine, whereas F8-IL4 did not inhibit colitis and F8-IL13 worsened the inflammatory conditions.
    Inflammatory Bowel Diseases 05/2015; 21(8). DOI:10.1097/MIB.0000000000000440 · 4.46 Impact Factor
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    ABSTRACT: The intratumoral injection of cytokines, in particular IL2, has shown promise for cutaneous melanoma patients with unresectable disease or continuous recurrence despite surgery. We recently reported that the intralesional injection of L19-IL2, an immunocytokine combining IL2 and the human monoclonal antibody fragment L19, resulted in efficient regional control of disease progression, increased time to distant metastasis and evidence of effect on circulating immune cell populations. We have also shown in preclinical models of cancer a remarkable synergistic effect of the combination of L19-IL2 with L19-TNF, a second clinical-stage immunocytokine, based on the same L19 antibody fused to TNF. Here, we describe the results of a phase II clinical trial based on the intralesional administration of L19-IL2 and L19-TNF in patients with stage IIIC and IVM1a metastatic melanoma, who were not candidate to surgery. In 20 efficacy-evaluable patients, 32 melanoma lesions exhibited complete responses upon intralesional administration of the two products, with mild side effects mainly limited to injection site reactions. Importantly, we observed complete responses in 7/13 (53.8 %) non-injected lesions (4 cutaneous, 3 lymph nodes), indicating a systemic activity of the intralesional immunostimulatory treatment. The intralesional administration of L19-IL2 and L19-TNF represents a simple and effective method for the local control of inoperable melanoma lesions, with a potential to eradicate them or make them suitable for a facile surgical removal of the residual mass.
    Cancer Immunology and Immunotherapy 05/2015; 64(8). DOI:10.1007/s00262-015-1704-6 · 3.94 Impact Factor
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    ABSTRACT: There is increasing interest in the site-directed pharmacodelivery of therapeutic payloads to the tumor site using antibodies as transport vehicles. Here, we investigated the efficacy of L19-IL2, an antibody-cytokine fusion protein that specifically delivers IL-2 to the tumor site by homing to the extra-domain B of fibronectin (EDB-Fn) expressed on tumor-associated blood vessels, against mantle cell lymphoma (MCL) in mice. L19-IL2 was shown to selectively localize at lymphoma lesions in vivo and to mediate significant lymphoma growth retardation, which was potentiated by co-administration of the anti-CD20 antibody rituximab. When co-injected with rituximab, L19-IL2 induced complete remissions of localized MCL xenografts in 6/8 mice (75%), whereas the combination of rituximab and equivalent doses of non-targeted IL-2 only slightly delayed tumor growth. In disseminated MCL, combination therapy with L19-IL2 and rituximab exhibited a significant survival benefit over treatment with IL-2 and rituximab and completely eradicated the disease in 2/7 cases (28.6%). Mechanistically, histological analyses of post-therapeutic lymphoma tissues revealed a strong intratumoral accumulation of macrophages and natural killer cells after a single dose of the immunocytokine, whereas L19-IL2 had no significant impact on microvessel density or on tissue penetration of co-injected rituximab. Collectively, these results provide the scientific rationale for the clinical evaluation of L19-IL2 in combination with anti-CD20 immunotherapy in patients with MCL. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Leukemia research 04/2015; 39(7). DOI:10.1016/j.leukres.2015.04.005 · 2.35 Impact Factor
  • Jörg Scheuermann · Dario Neri ·

    Current opinion in chemical biology 04/2015; 26. DOI:10.1016/j.cbpa.2015.03.014 · 6.81 Impact Factor
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    ABSTRACT: Endometriosis is caused by the displacement of endometrium outside the uterus contributing heavily to infertility and debilitating pelvic pain. Ectopic adhesion and growth are believed to occur under the influence of a favorable hormonal environment and immunological factors. The objective of this study is to analyze the effect of a targeted therapy with an antibody-based pharmacodelivery of interleukin 4 (F8-IL4) in a mouse model of experimentally induced endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4). Twelve days after disease induction, the lesions were isolated. A significant reduction in the number of total lesions/mouse and in the total volume of lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P = .029 and P = .006, respectively), while no difference was found between KSF-IL4-treated mice and their controls. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Expression of genes involved in cell adhesion, extracellular matrix invasion, and neovascularization was significantly downregulated in F8-IL4-treated mice compared to their controls (integrin β1: P = .02; metalloproteinase [MMP] 3: P = .02; MMP9: P = .04; vascular endothelial growth factor: P = .04). Gene expression of inflammatory cytokines (tumor necrosis factor α, IL1β, IL1α, and IL6) did not vary in the ectopic lesions isolated from F8-IL4-treated mice compared to their controls. Immunohistochemistry demonstrated a significantly reduced expression of E-cadherin and β-catenin in the lesions of mice treated with F8-IL4. Our results show that the antibody-mediated targeted delivery of IL4 inhibits the development of endometriosis in a syngeneic mouse model by likely impairing adhesion, invasion, and vascularization of the ectopic endometrium. © The Author(s) 2015.
    Reproductive sciences (Thousand Oaks, Calif.) 04/2015; 22(9). DOI:10.1177/1933719115578930 · 2.23 Impact Factor
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    ABSTRACT: Parallel affinity screening of a DNA-encoded chemical library against rat, bovine and human serum albumin allowed the identification of small-molecule ligands with distinctive binding specificities to the individual proteins.
    Chemical Communications 03/2015; 51(38). DOI:10.1039/c5cc01230a · 6.83 Impact Factor

Publication Stats

12k Citations
1,953.06 Total Impact Points


  • 2008-2015
    • ETH Zurich
      • • Institute of Pharmaceutical Sciences
      • • Department of Chemistry and Applied Biosciences
      Zürich, Zurich, Switzerland
    • National Research Council
      • Institute of Biomedical Technologies ITB
      Roma, Latium, Italy
  • 1997-2015
    • Eawag: Das Wasserforschungs-Institut des ETH-Bereichs
      Duebendorf, Zurich, Switzerland
  • 2014
    • Azienda Ospedaliera Universitaria Senese
      Siena, Tuscany, Italy
  • 2004
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 2002
    • Paul Scherrer Institut
      • Laboratory of Biomolecular Research
      Филлиген, Aargau, Switzerland
  • 1997-2000
    • Università degli Studi di Siena
      • Department of Medicine, Surgery and Neuroscience
      Siena, Tuscany, Italy
  • 1991-1998
    • Hochschule für Technik Zürich
      Zürich, Zurich, Switzerland