Cantore Alessio Ricercatore a tempo determinato juniorMedicinaNIO/17 Istologia

Biografia

Pubblicazioni

English version

Biografia

Titoli di studio

Laurea in Biotecnologie – 2004 – Università di Bologna – 110/110 e lode.

Laurea specialistica in Biotecnologie mediche, molecolari e cellulari – 2006 – Università “Vita Salute” San Raffaele – 110/110 e lode.

Dottorato di Ricerca in Biologia cellulare e molecolare – 2013 – Università “Vita Salute” San Raffaele e “Open University”, Inghilterra.

Esperienze lavorative

Dal 2017

Università “Vita Salute” San Raffaele

Ricercatore di Istologia, Facoltà di Medicina e Chirurgia.

Dal 2016

“Project Leader”

Istituto San Raffaele – Telethon per la Terapia Genica (SR-Tiget)

Dal 2013 al 2015

Borsista post-dottorato

Istituto San Raffaele – Telethon per la Terapia Genica (SR-Tiget)

Laboratorio Prof. Luigi Naldini

Dal 2008 al 2012

Dottorando presso Istituto San Raffaele – Telethon per la Terapia Genica (SR-Tiget)

Laboratorio Prof. Luigi Naldini

Dal 2005 al 2007

Studente di tesi di laurea specialistica e borsista post-laurea

Istituto San Raffaele – Telethon per la Terapia Genica (SR-Tiget)

Laboratorio Prof. Luigi Naldini

Nel 2004

Studente di tesi

Università di Bologna, Dipartimento di Istologia

Laboratorio Prof. Gianpaolo Bagnara

Partecipazione ad associazioni professionali

Membro della Società Americana di Terapia Genica e Cellulare dal 2007, della Società Europea di Terapia Genica dal 2009, della Società Internazionale di Terapia Genica e Cellulare dal 2017.

 

Relatore invitato

ESGCT – ISSCR Joint Meeting – Lausanne, 2018

“World Federation of Hemophilia” – Glasgow, 2018

“US National Hemophilia Foundation” – Washington, 2018, 2016, 2014

“Winter School” in Biotecnologie – Università di Perugia, 2017

 

Brevetti

Vector Production. Inventori: Cantore A, Annoni A, Milani M, Naldini L. 2018. Numero: P114659GB

Vector Production. Inventori: Cantore A, Lombardo A, Naldini L. 2014. Numero: WO2016009326.

Gene Vector for inducing transgene-specific immune tolerance. Inventori: Cantore A, Annoni A, Naldini L, Roncarolo MG. 2008. Numero: WO2010055413.

Premi:

– 7 “Travel Grant Awards” da Società Americana di Terapia Genica e Cellulare – 2010, 2012, 2014, 2016, 2017, da Società Europea di Terapia Genica e Cellulare nel 2016 e da Società Europea di Ematologia nel 2014.

– Best Translational Paper Award da Istituto Scientifico San Raffaele 2015

– Giuseppe Bigi Memorial Abstract Award dalla Società Americana di Ematologia nel 2017

Attività di ricerca:

La terapia genica sta vivendo un rinnovato interesse e sta emergendo come opzione terapeutica realistica per diverse malattie, come evidenziato anche dalla recente autorizzazione al commercio di diversi prodotti di terapia genica. Il fegato è un organo bersaglio molto rilevante per la terapia genica, in virtù della sua elevata attività metabolica e secretoria, dell’abbondante afflusso di sangue e della vasta microvascolatura permeabile, che facilita l’accesso di particelle virali e non virali dal circolo sanguigno agli epatociti. Il fegato è anche all’origine di molte malattie ereditarie e acquisite, tra cui malattie metaboliche, da accumulo lisosomiale e carenze di proteine ​​plasmatiche, come l’emofilia.

I vettori lentivirali (LV) sono veicoli attraenti per la terapia genica diretta al fegato per merito del loro potenziale di trasferimento genico stabile dopo una singola somministrazione endovenosa e della bassa prevalenza di immunità contro le componenti del vettore nell’uomo.

I nostri interessi di ricerca spaziano dall’ingegneria genetica di LV, alla biologia e alle applicazioni del trasferimento genico diretto dal fegato. In particolare studiamo le interazioni di LV con il sistema immunitario innato e altri tipi di cellule incontrate durante il viaggio dal sangue al fegato e studiamo il mantenimento del trasferimento genico in seguito alla proliferazione degli epatociti dovuta alla crescita dell’organo, al turnover fisiologico o a danni tessutali, al fine di progettare LV atti al trasferimento genico efficiente, duraturo e sicuro negli epatociti e valutare questi LV in modelli animali di emofilia e altre malattie genetiche o acquisite del metabolismo, con l’obiettivo finale di sviluppare nuovi prodotti di terapia avanzata per pazienti sia pediatrici, sia adulti. In collaborazione con altri gruppi di SR-Tiget, studiamo la risposta immunitaria al trasferimento genico al fegato e l’impatto dell’integrazione di LV, al fine di favorire tolleranza immunitaria al transgene e di ridurre al minimo i rischi di perturbazioni genomiche indotte da LV e mutagenesi inserzionale nel ricevente.

Pubblicazioni

Original Research Articles

Milani M, Annoni A, Bartolaccini S, Biffi M, Russo F, Di Tomaso T, Raimondi A, Lengler J, Holmes MC, Scheiflinger F, Lombardo A, Cantore A*, Naldini L*. Genome editing for scalable production of alloantigen-free lentiviral vectors for in vivo gene therapy. EMBO Mol Med. 2017 Aug 23. *Co-last authors.

Akbarpour M*, Goudy KS*, Cantore A, Russo F, Sanvito F, Naldini L, Annoni A, Roncarolo MG. Insulin B 9-23 Gene Transfer to Hepatocytes Protects from Type 1 Diabetes by Inducing Ag-Specific FoxP3+ Regulatory T Cells. Science Translational Medicine, 2015 May 27;7(289):289ra81. *Equal contribution.

Cantore A*, Ranzani M*, Bartholomae C, Volpin M, Della Valle P, Sanvito F, Sergi Sergi L, Gallina P, Benedicenti F, Bellinger D, Raymer R, Merricks E, Bellintani F, Martin S, Doglioni C, D’Angelo A, VandenDriessche T. Chuah M, Schmidt M, Nichols T, Montini E, Naldini L. Liver-Directed Lentiviral Gene Therapy in a Dog Model of Hemophilia B. Science Translational Medicine, 2015 Mar 4;7(277):277ra28. *Equal contribution.

Annoni A*, Cantore A*, Della Valle P, Goudy K, Akbarpour M, Russo F, Bartolaccini S, D’Angelo A, Roncarolo MG, Naldini L. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice. EMBO Mol Med. 2013 Nov;5(11):1684-97. *Equal contribution. 

Cantore A*, Nair N*, Della Valle P, Di Matteo M, Màtrai J, Sanvito F, Brombin C, Di Serio C, D’Angelo A, Chuah M, Naldini L, Vandendriessche T. Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice. Blood. 2012 Nov 29;120(23):4517-20. *Equal contribution.

Lombardo A, Cesana D, Genovese P, Di Stefano B, Provasi E, Colombo DF, Neri M, Magnani Z, Cantore A, Lo Riso P, Damo M, Pello OM, Holmes MC, Gregory PD, Gritti A, Broccoli V, Bonini C, Naldini L. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods. 2011 Aug 21;8(10):861-9.

Mátrai J*, Cantore A*, Bartholomae CC*, Annoni A*, Wang W, Acosta-Sanchez A, Samara-Kuko E, De Waele L, Ma L, Genovese P, Damo M, Arens A, Goudy K, Nichols TC, von Kalle C, L Chuah MK, Roncarolo MG, Schmidt M, Vandendriessche T, Naldini L. Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk. Hepatology. 2011 May;53(5):1696-707. *Equal contribution.

 

Annoni A*, Brown BD*, Cantore A, Sergi Sergi L, Naldini L, Roncarolo MG. In vivo delivery of a microRNA regulated transgene induces antigen-specific regulatory T cells and promotes immunological tolerance. Blood. 2009 Dec 10;114(25):5152-61. *Equal contribution. 

Brown BD*, Gentner B*, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L.  Endogenous microRNAs can be broadly exploited to regulate transgene expression according to tissue, lineage, and differentiation state. Nature Biotechnology. 2007 Dec 25;(12):1457-67. *Equal contribution.

Brown BD, Cantore A, Annoni A, Sergi Sergi L, Lombardo A, Della Valle P, D’Angelo A, Naldini L. A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood. 2007 Dec 15;110(13):4144-52.

English version

GRAPHICAL SKETCH

NAME

 

CANTORE Alessio POSITION TITLE Project Leader, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy Assistant Professor of Tissue Biology, “Vita Salute San Raffaele” University, Milan, Italy

 

EDUCATION/TRAINING

 

INSTITUTION DEGREE YEAR(s) FIELD OF STUDY

University of Bologna, IT B.Sc. (Summa cum Laude) 2004 Biotechnology

“Vita Salute San Raffaele” University,

Milan, IT M.Sc. (Summa cum Laude) 2006 Medical Biotechnology

“Vita Salute San Raffaele” University,

Milan, IT – Open University, London,

UK Ph.D. 2008-2012 Cellular and Molecular Biology

San Raffaele Telethon Institute for

Gene Therapy (Luigi Naldini’s

laboratory), Milan, IT Post-doctoral Training 2013-2015 Lentiviral Vectors and Gene Therapy

 

EMPLOYMENT AND EXPERIENCE

 

2004 Bachelor Student at Prof. Gianpaolo Bagnara’s laboratory, University of Bologna, Department of Histology, Embryology and Applied Cellular Biology.

2005-06 Master Student at Prof. Luigi Naldini’s laboratory, San Raffaele Telethon Institute for Gene Therapy.

2007 Research Fellow at Prof. Luigi Naldini’s laboratory, San Raffaele Telethon Institute for Gene Therapy.

2008-12 PhD Student in Cellular and Molecular Biology at “Vita-Salute San Raffaele” University, Milan, Italy, and Open University, London, UK. Host laboratory: Prof. Luigi Naldini’s laboratory, San Raffaele Telethon Institute for Gene Therapy.

2013-15 Post-doctoral Fellow at Prof. Luigi Naldini’s laboratory, San Raffaele Telethon Institute for Gene Therapy.

Since 2016 Project Leader at the San Raffaele Telethon Institute for Gene Therapy.

Since 2017 Assistant Professor of Tissue Biology, “Vita Salute San Raffaele” University

 

PROFESSIONAL ACTIVITIES

 

Scientific Memberships

- Member of: American Society of Gene and Cell Therapy (ASGCT), European Society of Gene and Cell Therapy (ESGCT), International Society of Cell and Gene Therapy (ISCT).

Mentoring and Teaching

- Currently mentoring 2 Ph.D. students (International Graduate School in Molecular Medicine, “Vita Salute San Raffaele” University), a Master student (Biotechnology, University of Trieste) and a M.D. student (“Vita Salute San Raffaele” University).

- Mentored 3 Master students (Medical Biotechnology, “Vita Salute San Raffaele” University).

- Contributing lectures for “Cell and Gene Therapy” course for students in the biotechnology degree at “Vita-Salute San Raffaele” University, Milan, Italy – since 2008.

- Teacher of the “Histology” course for students in the medical and biotechnology degree at “Vita-Salute San Raffaele” University, Milan, Italy – since 2011.

Reviewer

- Scientific reviewer in 2 patent review sessions at Telethon Foundation.

- Reviewer of manuscripts submitted to Human Gene Therapy, Scientific Reports, Haematologica.

Invited Speaker

- Communicating Medicine of the Future – A course for scientific journalists – June 2018

- World Federation of Hemophilia World Congress – May 2018

- US National Hemophilia Foundation 12th, 13th, 14th Workshop on Novel Technologies and Gene Transfer for Hemophilia – October 2014, October 2016, February 2018

- Spark Therapeutics scientific seminar – February 2018

- Winter School on Biotechnology, University of Perugia – January 2017

Other activities

- Member of the Organizing Committee of International Society of Cell Therapy regional meeting – Florence 12-14th September 2018

- Member of the PhD Students Invited Lecture Committee (2009-2011)

- Contributor for BiotechBook, a popular science website for high-school students (2008).

 

PATENTS

 

IL2 Gene Therapy in HBV. Inventors: Iannacone M, Guidotti L, Ostuni R, Cantore A, Naldini L. Priority date 28 May 2019 (UK Patent Application No. 1907493.9)

Vector Production (CD47 free). Inventors: Cantore A, Annoni A, Milani M, Naldini L. Priority Date 16 May 2018 (UK patent application No. 1807945.9.)

Vector Production (MHC free). Inventors: Cantore A, Lombardo A, Naldini L. Priority Date: 14 July 2014 (UK patent application No. 1412494.5). International Publication Number: WO2016009326.

Gene Vector for inducing transgene-specific immune tolerance. Inventors: Cantore A, Annoni A, Naldini L, Roncarolo MG. Priority Date: 12 November 2008 (US provisional No. 61/113,616). International Publication Number: WO2010055413. US patent application No. 13/128,761 (status: pending). European patent granted No. EP2364362.

 

HONORS

 

Recipient of

- Excellence in Research Award from the American Society of Gene and Cell Therapy in 2019

- Young Investigator Award from the European Society of Gene and Cell Therapy in 2018

- Giuseppe Bigi Memorial Abstract Achievement Award from the American Society of Hematology in 2017

- 7 Meritorious Travel Grant Awards from the American Society of Gene and Cell Therapy in 2010, 2012, 2014, 2016, 2017, from the European Society of Gene and Cell Therapy in 2016 and from the European Hematology Association in 2014

- Best Translational Paper Award from the San Raffaele Scientific Institute in 2015

 

SCIENTIFIC ACTIVITIES

 

Since 2007, I have published 11 original research articles in peer-reviewed international scientific journals, of which 4 as first author, 4 as second author, 2 as co-last author. Collectively my publications have been cited 1098 times (as of May 2019). Scopus “h” index: 9.

My scientific interest lies in gene therapy and stem cells as I am convinced that these pillars of regenerative medicine will have a broad impact on human health. I have started my laboratory training in Prof. Gianpaolo Bagnara’s laboratory at the University of Bologna, where I contributed to the isolation of putative human mesenchymal stem cell populations from fetal membrane and characterized their phenotype and in vitro differentiation potential. I have continued my training as undergraduate student at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) under the supervision of Prof. Luigi Naldini and Dr. Brian D. Brown (currently Associate Professor at Mount Sinai School of Medicine), where I contributed to the optimization of microRNA-regulated lentiviral vector design, with a focus on the factors that govern microRNA-mediated regulation in vitro and to the first in vivo application of novel hepatocyte-targeted microRNA-regulated lentiviral vectors in a hemophilia B mouse model. I have then been admitted in the competitive international Ph.D. Program in Cellular and Molecular Biology jointly run by “Vita-Salute San Raffaele” University, Milan and the Open University, London, under the supervision of Prof. Luigi Naldini (SR-Tiget), Prof. Thierry VandenDriessche (Free University of Brussels) and Prof. Maria Grazia Roncarolo (currently Chief of the Division of Pediatric Translational and Regenerative Medicine at Stanford School of Medicine). During my Ph.D., I undertook comprehensive studies aimed at developing liver-directed gene therapy with lentiviral vectors, by evaluating its feasibility, safety and efficacy, improving its potency, strengthening and broadening its possible applications, utilizing both small and large animal models. I have been learned to peer review, write reports and assess

scientific literature. As a Post-doctoral fellow, I decided to continue and expand the research project conducted during my Ph.D., concerning i) the application of liver-directed lentiviral gene therapy to hemophilia A and ii) the generation and characterization of lentiviral producer cell lines through genome editing technologies. I have become progressively independent in the design, conduction and interpretation of research and have coordinated the activities of several technicians and students. I have successfully collaborated with colleagues at SR-Tiget. I have actively contributed to establish or consolidate collaborations within the San Raffaele Scientific Institute and externally, both at academic institutions and at contract manufacturing organizations. I have contributed to grant writing and to the negotiations of a broad-scope strategic alliance between SR-Tiget and the biotechnology company Biogen, aimed to jointly develop lentiviral gene therapy for hemophilia A and B. I have been then promoted Project Leader at SR-Tiget for the results achieved and the responsibility taken within the above mentioned alliance and I am currently co-principal investigator of the liver gene therapy research project and I supervise a group of 6 people. As Project Leader, my efforts have exploited gene targeting to generate immune stealth lentiviral vectors with improved safety and efficacy for in vivo administration and culminated in designing and supervising the first studies of in vivo intravenous administration of lentiviral vectors in non-human primates, reported in 2 manuscript assembled under my co-senior authorship.

 

SCIENTIFIC PRODUCTION

 

Original Research Articles

 

Milani M, Annoni A, Moalli F, Liu T, Cesana D, Calabria A, Bartolaccini S, Biffi M, Russo F, Visigalli I, Raimondi A, Patarroyo-White S, Drager D, Cristofori P, Ayuso E, Montini E, Peters R, Iannacone M, Cantore A*, Naldini L*. Phagocytosis-Shielded Lentiviral Vectors Improve Liver Gene Therapy in Non Human Primates. Sci Transl Med. 2019 May 22;11(493). pii: eaav7325. *Co-last, co-corresponding authors.

 

Milani M, Annoni A, Bartolaccini S, Biffi M, Russo F, Di Tomaso T, Raimondi A, Lengler J, Holmes MC, Scheiflinger F, Lombardo A, Cantore A*, Naldini L*. Genome editing for scalable production of alloantigen-free lentiviral vectors for in vivo gene therapy. EMBO Mol Med, 2017 Aug 23. *Co-last authors.

 

Akbarpour M*, Goudy KS*, Cantore A, Russo F, Sanvito F, Naldini L, Annoni A, Roncarolo MG. Insulin B 9-23 gene transfer to hepatocytes protects from type 1 diabetes by inducing Ag-specific FoxP3+ regulatory T cells. Sci Transl Med, 2015 May 27;7(289):289ra81. *Equal contribution.

 

Cantore A*, Ranzani M*, Bartholomae C, Volpin M, Della Valle P, Sanvito F, Sergi Sergi L, Gallina P, Benedicenti F, Bellinger D, Raymer R, Merricks E, Bellintani F, Martin S, Doglioni C, D’Angelo A, VandenDriessche T. Chuah M, Schmidt M, Nichols T, Montini E, Naldini L. Liver-directed lentiviral gene therapy in a dog model of hemophilia B. Sci Transl Med, 2015 Mar 4;7(277):277ra28. *Equal contribution.

 

Annoni A*, Cantore A*, Della Valle P, Goudy K, Akbarpour M, Russo F, Bartolaccini S, D'Angelo A, Roncarolo MG, Naldini L. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice. EMBO Mol Med. 2013 Nov;5(11):1684-97. *Equal contribution.

 

Cantore A*, Nair N*, Della Valle P, Di Matteo M, Màtrai J, Sanvito F, Brombin C, Di Serio C, D'Angelo A, Chuah M, Naldini L, Vandendriessche T. Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice. Blood. 2012 Nov 29;120(23):4517-20. *Equal contribution.

 

Lombardo A, Cesana D, Genovese P, Di Stefano B, Provasi E, Colombo DF, Neri M, Magnani Z, Cantore A, Lo Riso P, Damo M, Pello OM, Holmes MC, Gregory PD, Gritti A, Broccoli V, Bonini C, Naldini L. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods. 2011 Aug 21;8(10):861-9.

 

Mátrai J*, Cantore A*, Bartholomae CC*, Annoni A*, Wang W, Acosta-Sanchez A, Samara-Kuko E, De Waele L, Ma L, Genovese P, Damo M, Arens A, Goudy K, Nichols TC, von Kalle C, L Chuah MK, Roncarolo MG, Schmidt M, Vandendriessche T, Naldini L. Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk. Hepatology. 2011 May;53(5):1696-707. *Equal contribution.

 

Annoni A*, Brown BD*, Cantore A, Sergi Sergi L, Naldini L, Roncarolo MG. In vivo delivery of a microRNA regulated transgene induces antigen-specific regulatory T cells and promotes immunological tolerance. Blood. 2009 Dec 10;114(25):5152-61. *Equal contribution.

 

Brown BD*, Gentner B*, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L. Endogenous microRNAs can be broadly exploited to regulate transgene expression according to tissue, lineage, and differentiation state. Nature Biotechnol. 2007 Dec 25;(12):1457-67. *Equal contribution.

 

Brown BD, Cantore A, Annoni A, Sergi Sergi L, Lombardo A, Della Valle P, D'Angelo A, Naldini L. A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood. 2007 Dec 15;110(13):4144-52.

 

Review Articles

 

Annoni A, Gregori S, Naldini L, Cantore A. Modulation of immune responses in lentiviral vector-mediated gene transfer. Cell Immunol. 2018

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