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Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature

English title Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature
Applicant Neri Dario
Number 163479
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pharmazeutische Wissenschaften ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Experimental Cancer Research
Start/End 01.10.2015 - 30.09.2018
Approved amount 692'014.00
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All Disciplines (2)

Discipline
Experimental Cancer Research
Cellular Biology, Cytology

Keywords (1)

Vascular Targeting

Lay Summary (Italian)

Lead
Numerose patologie, tra cui vari tipi di tumori, sono caratterizzati dalla presenza di vasi sanguigni neo-formati, che differiscono a livello molecolare dai vasi sanguigni dei tessuti normali. In particolare, alcune proteine situate nelle immediate vicinanze dei vasi sanguigni dei tessuti malati contengono delle strutture addizionali (in termini tecnici, degli “extra dominii”, generati mediante un processo di splicing alternativo), che possono servire da bersaglio per la generazione di farmaci a base di anticorpi monoclonali. Lo scopo principale del progetto consiste nella generazione e ottimizzazione di farmaci a base di anticorpi, capaci di localizzarsi in maniera selettiva attorno ai vasi sanguigni neo-formati nei tumori e in altre patologie importanti, quali l’artrite reumatoide e la colite ulcerosa.
Lay summary

Isoforme di splicing della fibronettina e della tenascina-C rappresentano alcuni dei bersagli molecolari piu’ interessanti, per una veicolazione selettiva di farmaci nei tumori o in altre patologie (quali l’artrite reumatoide e la colite ulcerosa). Tali proteine sono virtualmente assenti nei tessuti sani, ma sono estremamente abbondanti in tessuti in rapido rimodellamento. Anticorpi e altri tipi di molecole leganti possono essere utilizzati per veicolare molecole bioattive (e.g., farmaci citotossici o citochine) nella zona malata, aumentandone l’efficacia e diminuendo gli effetti collaterali. In questo progetto, continueremo la nostra attivita’ di ricerca nel settore, iniziata oltre 20 anni fa, cercando di migliorare l’efficacia dei nuovi farmaci “mirati” a base di anticorpi. Aspetti particolarmente rilevanti del progetto includono:

  1. la generazione di nuove proteine di fusione a base di anticorpi monoclonali e citochine, ad elevatissima selettivita’ terapeutica
  2. lo studio del meccanismo d’azione di tali farmaci biotecnologici
  3. lo studio di combinazioni terapeutiche particolarmente efficaci in modelli murini
  4. lo sviluppo di nuove molecole leganti: sia quelle a base di anticorpi che quelle a base di piccole molecole organiche

 

Direct link to Lay Summary Last update: 26.09.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
In Vivo Antitumor Activity of a Novel Acetazolamide–Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas
Cazzamalli Samuele, Figueras Eduard, Pethő Lilla, Borbély Adina, Steinkühler Christian, Neri Dario, Sewald Norbert (2018), In Vivo Antitumor Activity of a Novel Acetazolamide–Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas, in ACS Omega, 3(11), 14726-14731.
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
De Luca Roberto, Neri Dario (2018), 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, in Cancer Immunology, Immunotherapy, 67(9), 1381-1391.
Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2
Cazzamalli Samuele, Ziffels Barbara, Widmayer Fontaine, Murer Patrizia, Pellegrini Giovanni, Pretto Francesca, Wulhfard Sarah, Neri Dario (2018), Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2, in Clinical Cancer Research, 24(15), 3656-3667.
A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition
Favalli Nicholas, Biendl Stefan, Hartmann Marco, Piazzi Jacopo, Sladojevich Filippo, Gräslund Susanne, Brown Peter J., Näreoja Katja, Schüler Herwig, Scheuermann Jörg, Franzini Raphael, Neri Dario (2018), A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition, in ChemMedChem, 13(13), 1303-1307.
DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information
Neri Dario, Lerner Richard A. (2018), DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information, in Annual Review of Biochemistry, 87(1), 479-502.
DNA-encoded chemical libraries - achievements and remaining challenges
Favalli Nicholas, Bassi Gabriele, Scheuermann Jörg, Neri Dario (2018), DNA-encoded chemical libraries - achievements and remaining challenges, in FEBS Letters, 592(12), 2168-2180.
A novel dual-cytokine–antibody fusion protein for the treatment of CD38-positive malignancies
De Luca Roberto, Kachel Paul, Kropivsek Klara, Snijder Berend, Manz Markus G, Neri Dario (2018), A novel dual-cytokine–antibody fusion protein for the treatment of CD38-positive malignancies, in Protein Engineering, Design and Selection, 31(5), 173-179.
Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold
Li Yizhou, De Luca Roberto, Cazzamalli Samuele, Pretto Francesca, Bajic Davor, Scheuermann Jörg, Neri Dario (2018), Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold, in Nature Chemistry, 10(4), 441-448.
Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone for the reduction of inflammation in arthritis
Schmid Anja Sophie, Hemmerle Teresa, Pretto Francesca, Kipar Anja, Neri Dario (2018), Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone for the reduction of inflammation in arthritis, in Rheumatology, 57(4), 748-755.
Novel antibody-cytokine fusion proteins featuring granulocyte-colony stimulating factor, interleukin-3 and interleukin-4 as payloads
Schmid Anja Sophie, Tintor Diana, Neri Dario (2018), Novel antibody-cytokine fusion proteins featuring granulocyte-colony stimulating factor, interleukin-3 and interleukin-4 as payloads, in Journal of Biotechnology, 271, 29-36.
Membranal and Blood-Soluble HLA Class II Peptidome Analyses Using Data-Dependent and Independent Acquisition
Ritz Danilo, Sani Emiliano, Debiec Hanna, Ronco Pierre, Neri Dario, Fugmann Tim (2018), Membranal and Blood-Soluble HLA Class II Peptidome Analyses Using Data-Dependent and Independent Acquisition, in PROTEOMICS, 1700246-1700246.
Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer without establishing protective immunity
Ziffels Barbara, Pretto Francesca, Neri Dario (2018), Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer without establishing protective immunity, in Immunotherapy, (3), 177-188.
Chemically Defined Antibody– and Small Molecule–Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis
Cazzamalli Samuele, Dal Corso Alberto, Widmayer Fontaine, Neri Dario (2018), Chemically Defined Antibody– and Small Molecule–Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis, in Journal of the American Chemical Society, (5), 1617-1621.
Potency-matched Dual Cytokine–Antibody Fusion Proteins for Cancer Therapy
De Luca Roberto, Soltermann Alex, Pretto Francesca, Pemberton-Ross Catherine, Pellegrini Giovanni, Wulhfard Sarah, Neri Dario (2017), Potency-matched Dual Cytokine–Antibody Fusion Proteins for Cancer Therapy, in Molecular Cancer Therapeutics, (11), 2442-2451.
Targeted Delivery of Cytotoxic Drugs: Challenges, Opportunities and New Developments
Cazzamalli Samuele, Corso Alberto Dal, Neri Dario (2017), Targeted Delivery of Cytotoxic Drugs: Challenges, Opportunities and New Developments, in CHIMIA International Journal for Chemistry, (10), 712-715.
Data-Independent Acquisition of HLA Class I Peptidomes on the Q Exactive Mass Spectrometer Platform
Ritz Danilo, Kinzi Jonny, Neri Dario, Fugmann Tim (2017), Data-Independent Acquisition of HLA Class I Peptidomes on the Q Exactive Mass Spectrometer Platform, in PROTEOMICS, (19), 1700177-1700177.
A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo
Dal Corso Alberto, Gébleux Rémy, Murer Patrizia, Soltermann Alex, Neri Dario (2017), A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo, in Journal of Controlled Release, 211-218.
Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody-Drug Conjugates
Dal Corso Alberto, Cazzamalli Samuele, Gebleux Remy, Mattarella Martin, Neri Dario (2017), Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody-Drug Conjugates, in BIOCONJUGATE CHEMISTRY, (7), 1826-1833.
Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8(+) T-cell Recognition of a Retroviral Antigen
Probst Philipp, Kopp Janine, Oxenius Annette, Colombo Mario P., Ritz Danilo, Fugmann Tim, Neri Dario (2017), Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8(+) T-cell Recognition of a Retroviral Antigen, in CANCER RESEARCH, (13), 3644-3654.
A Specific and Covalent JNK-1 Ligand Selected from an Encoded Self-Assembling Chemical Library
Zimmermann Gunther, Rieder Ulrike, Bajic Davor, Vanetti Sara, Chaikuad Apirat, Knapp Stefan, Scheuermann Jorg, Mattarella Martin, Neri Dario (2017), A Specific and Covalent JNK-1 Ligand Selected from an Encoded Self-Assembling Chemical Library, in CHEMISTRY-A EUROPEAN JOURNAL, (34), 8152-8155.
Intralesional treatment of metastatic melanoma: a review of therapeutic options
Weide Benjamin, Neri Dario, Elia Giuliano (2017), Intralesional treatment of metastatic melanoma: a review of therapeutic options, in CANCER IMMUNOLOGY IMMUNOTHERAPY, (5), 647-656.
Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries
Zimmermann Gunther, Li Yizhou, Rieder Ulrike, Mattarella Martin, Neri Dario, Scheuermann Jorg (2017), Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries, in CHEMBIOCHEM, (9), 853-857.
Quantitative PCR is a Valuable Tool to Monitor the Performance of DNA-Encoded Chemical Library Selections
Li Yizhou, Zimmermann Gunther, Scheuermann Joerg, Neri Dario (2017), Quantitative PCR is a Valuable Tool to Monitor the Performance of DNA-Encoded Chemical Library Selections, in CHEMBIOCHEM, (9), 848-852.
The MHC Class II Immunopeptidome of Lymph Nodes in Health and in Chemically Induced Colitis
Fugmann Tim, Sofron Adriana, Ritz Danilo, Bootz Franziska, Neri Dario (2017), The MHC Class II Immunopeptidome of Lymph Nodes in Health and in Chemically Induced Colitis, in The Journal of Immunology, (3), 1357-1364.
Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma
Cazzamalli Samuele, Corso Alberto Dal, Neri Dario (2017), Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma, in Journal of Controlled Release, 39-45.
A 99mTc-Labeled Ligand of Carbonic Anhydrase IX Selectively Targets Renal Cell Carcinoma In Vivo
Krall N., Pretto F., Mattarella M., Muller C., Neri D. (2016), A 99mTc-Labeled Ligand of Carbonic Anhydrase IX Selectively Targets Renal Cell Carcinoma In Vivo, in Journal of Nuclear Medicine, (6), 943-949.
Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to Renal Cell Carcinoma
Cazzamalli S., Dal Corso A., Neri D. (2016), Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to Renal Cell Carcinoma, in Molecular Cancer Therapeutics, (12), 2926-2935.
Antibody-Based Targeted Delivery of Interleukin-22 Promotes Rapid Clinical Recovery in Mice With DSS-Induced Colitis
Bootz Franziska, Ziffels Barbara, Neri Dario (2016), Antibody-Based Targeted Delivery of Interleukin-22 Promotes Rapid Clinical Recovery in Mice With DSS-Induced Colitis, in Inflammatory Bowel Diseases, (9), 2098-2105.
Automated screening for small organic ligands using DNA-encoded chemical libraries.
Decurtins W., Wichert M., Franzini R.M., Buller F., Stravs M.A., Zhang Y., Neri D., Scheuermann J. (2016), Automated screening for small organic ligands using DNA-encoded chemical libraries., in Nature Protocols, (11), 764-780.
Different tissue distribution properties for glycosylation variants of fusion proteins containing the p40 subunit of murine interleukin-12
Bootz F., Venetz D., Ziffels B., Neri D. (2016), Different tissue distribution properties for glycosylation variants of fusion proteins containing the p40 subunit of murine interleukin-12, in Protein Engineering Design and Selection, (10), 445-455.
DNA-encoded chemical libraries: foundations and applications in lead discovery
Zimmermann Gunther, Neri Dario (2016), DNA-encoded chemical libraries: foundations and applications in lead discovery, in Drug Discovery Today, (11), 1828-1834.
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
Ritz Danilo, Gloger Andreas, Weide Benjamin, Garbe Claus, Neri Dario, Fugmann Tim (2016), 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, in PROTEOMICS, 16(10), 1570-1580.
Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site
Kiefer Jonathan, Neri Dario (2016), Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site, in Immunological Reviews, 178-192.
Immunocytokines for cancer treatment: past, present and future
Neri Dario, Sondel Paul M (2016), Immunocytokines for cancer treatment: past, present and future, in Current Opinion in Immunology, 96-102.
Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions
Bootz Franziska, Neri Dario (2016), Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions, in Drug Discovery Today, (1), 180-189.
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
Gloger Andreas, Ritz Danilo, Fugmann Tim, Neri Dario (2016), 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, in Cancer Immunology, Immunotherapy, (11), 1377-1393.
Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries
Li Yizhou, Gabriele Elena, Samain Florent, Favalli Nicholas, Sladojevich Filippo, Scheuermann Jörg, Neri Dario (2016), Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries, in ACS Combinatorial Science, (8), 438-443.
Targeted Reconstitution of Cytokine Activity upon Antigen Binding using Split Cytokine Antibody Fusion Proteins
Venetz Dario, Koovely Danil, Weder Bruce, Neri Dario (2016), Targeted Reconstitution of Cytokine Activity upon Antigen Binding using Split Cytokine Antibody Fusion Proteins, in Journal of Biological Chemistry, (35), 18139-18147.
Antibody Format and Drug Release Rate Determine the Therapeutic Activity of Noninternalizing Antibody-Drug Conjugates
Gebleux R., Wulhfard S., Casi G., Neri D. (2015), Antibody Format and Drug Release Rate Determine the Therapeutic Activity of Noninternalizing Antibody-Drug Conjugates, in Molecular Cancer Therapeutics, (11), 2606-2612.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Workshop “Life Science Community”, SciForLife, Karolinska University Talk given at a conference Biologics: from academic idea to the clinic 12.09.2018 Stockholm, Sweden Neri Dario;
Buzzati-Traverso Lecture, EMBO Workshop on Enzymes, Biocatalysis and Chemical Biology Talk given at a conference From encoded combinatorial libraries to targeted therapeutics 12.09.2018 Pavia, Italy Neri Dario;
FEBS 2018 Congress Talk given at a conference From encoded libraries to clinical-stage targeted therapeutics 07.07.2018 Prague, Czech Republic Neri Dario;
European Congress of Biotechnology Talk given at a conference Antibody-cytokine fusions: a novel class of biopharmaceuticals for the treatment of cancer and of chronic inflammation 01.07.2018 Geneva, Switzerland Neri Dario;
Clinician Scientist Symposium on Translational Medicine Talk given at a conference Antibody-cytokine fusions for cancer therapy 29.06.2018 Berlin, Germany Neri Dario;
FOCIS-SITC Congress Talk given at a conference Engineered antibodies for cancer therapy 20.06.2018 San Francisco, United States of America Neri Dario;
Lecture at the Novartis Institute for Functional Genomics, Individual talk From encoded libraries to clinical-stage targeted therapeutics 18.06.2018 La Jolla, United States of America Neri Dario;
Postgraduate Course CAS Pharmaceuticals Talk given at a conference Quality aspects of therapeutic antibodies: Humira™ as a case study 07.06.2018 Basel, Switzerland Neri Dario;
Spring Meeting of the Swiss Society of Pharmacology and Toxicology Talk given at a conference Antibody-cytokine fusion proteins: from the bench to Phase III clinical trials 19.04.2018 Bern, Switzerland Neri Dario;
Pharma Horizonte 2018 Talk given at a conference Protein-based therapeutics: different classes, different properties and different development processes for biosimilars 12.04.2018 Fribourg, Switzerland Neri Dario;
Lecture at the Institute of Oncology Research (IOR), Universita’ della Svizzera Italiana Talk given at a conference Antibody-cytokine fusion proteins: a novel class of immunotherapeutics for the treatment of cancer and of chronic inflammation 22.03.2018 Bellinzona, Switzerland Neri Dario;
Second Annual Next-Generation Immuno-Oncology Congress Talk given at a conference Antibody-cytokine fusion proteins: a novel class of immunotherapeutics for the treatment of cancer and of chronic inflammation 14.03.2018 London, Great Britain and Northern Ireland Neri Dario;
From encoded combinatorial libraries to targeted therapeutics Individual talk Lecture at the Department of Pharmacy, University of Bologna 02.03.2018 Bologna, Italy Neri Dario;
ESMO Immuno Oncology Congress Talk given at a conference Kickstart the immune system with immunocytokines 08.12.2017 Geneva, Switzerland Neri Dario;
DTU Immunology Seminars Series Talk given at a conference From encoded combinatorial libraries to targeted therapeutics 24.11.2017 Copenhagen, Denmark Neri Dario;
Lecture at Merck Individual talk Antibody-cytokine fusions: turning “cold” tumors “hot” 06.11.2017 Boston, United States of America Neri Dario;
World Immunotherapy Congress Talk given at a conference Antibody-cytokine fusions for cancer therapy 31.10.2017 Basel, Switzerland Neri Dario;
Lecture at AstraZeneca Talk given at a conference From encoded combinatorial libraries to targeted therapeutics 02.10.2017 Mölndal, Sweden Neri Dario;
38th Max-Bergmann-Konferenz Talk given at a conference From encoded combinatorial libraries to targeted therapeutics 25.09.2017 Reutlingen, Germany Neri Dario;
Annual BMWZ Symposium, Centre of Biomolecular Drug Research, University of Hannover Talk given at a conference From encoded combinatorial libraries to targeted therapeutics 14.09.2017 Hannover, Germany Neri Dario;
SciForLife, Seminar Series Talk given at a conference From encoded combinatorial libraries to targeted therapeutics 11.09.2017 Uppsala, Sweden Neri Dario;
Lecture at GSK Vaccines Individual talk Antibody fusions for the therapy of cancer and of chronic inflammation 04.09.2017 Siena, Italy Neri Dario;
Lecture at Merck KgaA Talk given at a conference Next-generation antibody-cytokine fusions: from the bench to the clinic 28.08.2017 Darmstadt, Germany Neri Dario;
Fall One-Day Thematic Symposium of the SCT (Conjugates and Drug Discovery Chemistry: new challenges for targeted therapies) Talk given at a conference Antibody-Drug Conjugates and Small Molecule-Drug Conjugates: a comparative evaluation 07.07.2017 Paris, France Neri Dario;
Congress “Los Anticuerpos Monoclonales, el camino desde el laboratorio hasta el paciente“ Talk given at a conference Antibody-cytokine fusions for the treatment of cancer and of chronic inflammation: from the bench to the clinic 06.07.2017 Santander, Spain Neri Dario;
F.O.C.I.S. Congress Talk given at a conference Focus on Engineered Antibodies 13.06.2017 Chicago, United States of America Neri Dario;
Lecture at Seattle Genetics Individual talk Ligand-based drug delivery in cancer and in chronic inflammation 12.06.2017 Botham WA, United States of America Neri Dario;
5th Heidelberg Forum for Young Life Science Scientists Talk given at a conference Antibody-cytokine fusions: a novel class of biopharmaceuticals for the treatment of cancer and of chronic inflammation 09.06.2017 Heidelberg, Germany Neri Dario;
Lecture at the CNR Institute of Cell Biology Individual talk From encoded combinatorial libraries to targeted therapeutics 16.05.2017 Monterotondo, Italy Neri Dario;
Seminars in Translational Immunology (STIMM) Individual talk Antibody-cytokine fusion proteins: from the bench to the clinic 05.04.2017 Zürich, Switzerland Neri Dario;
14th Symposium on Pharmacokinetics and Drug Metabolism, Swedish Pharmaceutical Society Talk given at a conference Antibody-drug conjugates and small molecule-drug conjugates: a comparative evaluation 29.03.2017 Gothenburg, Sweden Neri Dario;
Immuno-Oncology Summit Europe Talk given at a conference Investigations into mechanisms of immune tumor rejection 20.03.2017 London, Great Britain and Northern Ireland Neri Dario;
Lecture at Bayer, Wuppertal Individual talk From encoded combinatorial libraries to targeted therapeutics 02.02.2017 Wuppertal, Germany Neri Dario;
Lecture at the University of Pavia Individual talk From encoded combinatorial libraries to targeted therapeutics 26.01.2017 Pavia, Italy Neri Dario;
Antibody Engineering & Therapeutics Talk given at a conference Antibody-cytokine fusion proteins for the therapy of cancer and of chronic inflammation 11.12.2016 San Diego, United States of America Neri Dario;
3rd ShanghaiTech-SIAIS Symposium Talk given at a conference DNA-encoded chemical libraries 07.11.2016 Shanghai, China Neri Dario;
5th Lilly Chemistry Symposium Talk given at a conference DNA-encoded chemical libraries: a tool for drug discovery 27.10.2016 El Escorial, Spain Neri Dario;
Lecture at Boehringer Ingelheim Individual talk Encoded combinatorial libraries for drug discovery 13.10.2016 Vienna, Austria Neri Dario;
Congress of the German Pharmaceutical Society Talk given at a conference Antibody-cytokine fusions for the therapy of cancer and of chronic inflammation: from the bench to Phase III clinical trials 04.10.2016 Munich, Germany Neri Dario;
Cardiovascular University training event Talk given at a conference Gli anticorpi monoclonali in cardiologia 20.09.2016 Milano, Italy Neri Dario;
PIVAC Congress Talk given at a conference Immunocytokines for cancer therapy: from the bench to the clinic 12.09.2016 Winchester, Great Britain and Northern Ireland Neri Dario;
EFMC-ISMC International Symposium Talk given at a conference DNA-encoded chemical libraries 28.08.2016 Manchester, Great Britain and Northern Ireland Neri Dario;
ISMB Symposium Talk given at a conference Ligand discovery and anti-cancer therapeutics: from the bench to the clinic 30.06.2016 London, Great Britain and Northern Ireland Neri Dario;
Satellite Symposium on the Managing Hypercholesterolemia: Beyond Current Treatment Options, SSC/SSCS-SSP Talk given at a conference Monoclonal antibodies: targeting the PCSK9 pathway 15.06.2016 Lausanne, Switzerland Neri Dario;
ETH Postgraduate CAS Course on Quality and GMP, Module 3 Individual talk Quality aspects of therapeutic antibodies: Humira™ as a case study 09.06.2016 Basel, Switzerland Neri Dario;
“Giornata Didattica”, Dottorato Regionale Pegaso in Biochemica e Biologia Molecolare Talk given at a conference Innovating targeting: the experience of Philogen from ligand discovery to Phase III clinical trials 19.05.2016 Siena, Italy Neri Dario;
6th European Workshop on Drug Synthesis Talk given at a conference DNA-encoded chemical libraries 15.05.2016 Siena, Italy Neri Dario;
Protein and Antibody Engineering Summit (PEGS) Talk given at a conference Immunocytokines for the treatment of cancer and of chronic inflammation 25.04.2016 Boston, United States of America Neri Dario;
Lecture at Roche, Basel (Switzerland) Individual talk From encoded libraries to targeted therapeutics 19.04.2016 Basel, Switzerland Neri Dario;
Lecture at Servier Individual talk From encoded libraries to targeted therapeutics 13.04.2016 Croissy-sur-Seine, France Neri Dario;
Cancer Biotherapeutics - Immuno Oncology Summit Europe Talk given at a conference Antibody-cytokine fusion proteins (immunocytokines) for targeted delivery: from bench to Phase III clinical trials 14.03.2016 London, Great Britain and Northern Ireland Neri Dario;
Lecture at the University of Aarhus (Denmark) Individual talk Armed antibodies for the treatment of cancer and of chronic inflammation 11.03.2016 Aarhus, Denmark Neri Dario;
Swiss Society of Pharmacology and Toxicology meeting “Fortschritte in der Pharmakologie”. Talk given at a conference Translationale Forschung in der Arzneimittelentwicklung 28.01.2016 Bern, Switzerland Neri Dario;
“Neurology and MS research” seminar series, Klinik für Neurologie, University Hospital Talk given at a conference Armed antibodies for the treatment of cancer and of chronic inflammation: from the bench to the clinic 20.01.2016 Zürich, Switzerland Neri Dario;
2nd CEE Hyperlipidemia Meeting Talk given at a conference Monoclonal antibodies – clinical experience 27.11.2015 Bratislava, Slovakia Neri Dario;
European Antibody Congress Talk given at a conference Armed antibodies for the treatment of cancer and of chronic inflammation: from the bench to the clinic 09.11.2015 Basel, Switzerland Neri Dario;
Keynote Lecture at the 1st Boston Symposium on Encoded Library Platforms Talk given at a conference Single-pharmacophore and dual-pharmacophore DNA-encoded chemical libraries: a comparative evaluation 06.11.2015 Boston, United States of America Neri Dario;
Protein and Antibody Engineering Summit (PEGS) Europe Talk given at a conference DNA-encoded chemical libraries for the isolation of high-affinity binding ligands: an alternative to antibodies 02.11.2015 Lisbon, Portugal Neri Dario;
19th International Conference on Human Antibodies & Hybridomas Talk given at a conference Engineering armed antibodies for cancer therapy: from the bench to the clinic 28.10.2015 Lausanne, Switzerland Neri Dario;
Cancer and Immunity: ask the Expert. Seminar Series at the University of Fribourg (Switzerland) Talk given at a conference Towards a cure for cancer: chemotherapy or immunotherapy? 15.10.2015 Friboug, Switzerland Neri Dario;
Seminar at the Department of Medicine, University of Fribourg (Switzerland), Talk given at a conference Armed antibodies for the treatment of cancer and of chronic inflammation: from the bench to the clinic 15.10.2015 Fribourg, Switzerland Neri Dario;
ECBS/ICBS Congress Talk given at a conference Armed antibodies and small molecule drug conjugates for cancer therapy 08.10.2015 Berlin, Germany Neri Dario;


Associated projects

Number Title Start Funding scheme
182003 Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature 01.10.2018 Project funding (Div. I-III)
144091 Understanding and exploiting the molecular targeting of tumor neo-vasculature 01.10.2012 Project funding (Div. I-III)
144091 Understanding and exploiting the molecular targeting of tumor neo-vasculature 01.10.2012 Project funding (Div. I-III)

Abstract

One avenue towards the development of more potent and selective anti-cancer therapeutics consists in the use of antibody derivatives (“armed antibodies”) for the targeted delivery of bioactive molecules to the tumor environment, helping spare normal tissues. In this context, the selective delivery of therapeutic agents to markers of pathology expressed around newly-formed blood vessels (“vascular targeting”) is particularly attractive, not only for cancer applications, but also for other indications (e.g., arthritis, blinding ocular disorders).We have previously generated and validated human monoclonal antibodies, capable of selective localisation to neo-vascular structures in vivo. In the next three years, we wish to extend our work, focusing on novel antibody-cytokine fusion proteins ("immunocytokines") and on novel versions of targeted cytotoxics (e.g., antibody-drug conjugates and small molecule drug-conjugates). In the field of immunocytokines, we see the greatest therapeutic opportunities in the investigation of combination modalities (e.g., combination of two cytokine payloads) and in the design of products with "activity on demand " (e.g., proteolytic activation at the site of disease, or conformational changes upon antigen binding).In the area of targeted cytotoxics, we will investigate the opportunity of releasing anti-cancer drugs at the tumor environment with non-internalising antibodies. In addition, we will study the possibility to by-pass antibodies with small organic ligands as pharmacodelivery vehicles.
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