Cantore Alessio Ricercatore a tempo determinato juniorMedicinaBIO/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 7/2020

“Group Leader”

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

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, della Società Europea di Terapia Genica, della Società Internazionale di Terapia Genica e Cellulare.

 

Relatore invitato

ESGCT – ISSCR Joint Meeting – Lausanne, 2018

“World Federation of Hemophilia” – Glasgow, 2018

“US National Hemophilia Foundation” – Washington, 2109, 2018, 2016, 2014

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

 

Brevetti

IL2 Gene Therapy in HBV. Inventori: Iannacone M, Guidotti L, Ostuni R, Cantore A, Naldini L. 2019. Numero: 1907493.9

Vector Production (CD47 free LV). Inventori: Cantore A, Annoni A, Milani M, Naldini L. 2018. Numero: P114659GB

Vector Production (MHC free LV). 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:

- “Young Investigator Award” dalla Società Europea di Terapia Genica e Cellulare nel 2018.

- “Excellence in Research” dalla Società Americana di Terapia Genica e Cellulare nel 2019.

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

- 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

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

EDUCATION/TRAINING

University of Bologna, IT, 2004

B.Sc. (Summa cum Laude) – Biotechnology

“Vita Salute San Raffaele” University, Milan, IT, 2006

M.Sc. (Summa cum Laude) – Medical Biotechnology

“Vita Salute San Raffaele” University, Milan, IT and

Open University, London, UK, 2008-2012

Ph.D. – Cellular and Molecular Biology

San Raffaele Telethon Institute for Gene Therapy (Luigi Naldini group), Milan, IT, 2013-2015

Post-doctoral training – 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.

2016-6/2020           Project Leader at the San Raffaele Telethon Institute for Gene Therapy.

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

Since 7/2020           Group Leader at the San Raffaele Telethon Institute for Gene Therapy

 

PROFESSIONAL ACTIVITIES

Scientific Memberships and Appointments

-    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).

-    Co-founder and consultant of GeneSpire, an innovative Start-up company aimed to develop liver-directed gene therapy for inherited metabolic diseases.

Teaching

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

-    Contributing lectures for “Cell and Gene Therapy” course for students in the biotechnology degree at “Vita-Salute San Raffaele” University, Milan, Italy – since 2009.

Mentoring

-    Currently mentoring 2 Ph.D. students (International Graduate School in Molecular Medicine, “Vita Salute San Raffaele” University).

-    Mentored 4 Master students (3 Medical Biotechnology, “Vita Salute San Raffaele” University; 1 Biotechnology, University of Trieste).

Reviewer

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

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

-    Abstract reviewer for ASGCT, ESGCT, ISCT

Invited Speaker

-    US National Hemophilia Foundation 12th, 13th, 14th, 15th Workshop on Novel Technologies and Gene Transfer for Hemophilia – October 2014, October 2016, February 2018, September 2019

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

-    World Federation of Hemophilia World Congress – May 2018

-    Spark Therapeutics scientific seminar – February 2018

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

Outreach and dissemination

-    Participated to several editions of the Telethon Marathon, the main Telethon Foundation fundraising campaign streamlined in the major Italian TV channels

-    Contributed interviews for popular science Italian TV shows

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 and AWARDS

Grants as Principal Investigator:

- GeneSpire Sponsored Research Agreement (2020-active, P.I.)

- Bioverativ/Sanofi Sponsored Research Agreement (2016-active, co-P.I.)

- Italian Ministry of Health “Giovani Ricercatori” 2019 (co-P.I., pending)

Recipient of:

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

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

- 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 12 original research articles and 3 reviews in peer-reviewed international scientific journals, of which 4 as first author, 4 as second author, 3 as last author. Collectively my publications have been cited 1250 times (as of Jul 2020). Scopus “h” index: 11.

My scientific interests lie 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 (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. 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 contributed to the negotiations of a strategic alliance between SR-Tiget and the biotechnology company Biogen, aimed to jointly develop lentiviral gene therapy for hemophilia A and B. 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. As Group Leader, I am currently responsible for the liver gene therapy research area and I supervise a group of 6 people. My research interests span between LV engineering, liver biology and the translational applications of liver-directed gene transfer and editing.

 

SCIENTIFIC PRODUCTION

Original Research Articles

Bénéchet AP, De Simone G, Di Lucia P, Cilenti F, Barbiera G, Le Bert N, Fumagalli V, Lusito E, Moalli F, Bianchessi V, Andreata F, Zordan P, Bono E, Giustini L, Bonilla WV, Bleriot C, Kunasegaran K, Gonzalez-Aseguinolaza G, Pinschewer DD, Kennedy PTF, Naldini L, Kuka M, Ginhoux F, Cantore A, Bertoletti A, Ostuni R, Guidotti LG, Iannacone M. Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming. Nature. 2019 Oct 2. PMID: 31582858

 

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. PMID: 31118293

Featured in: https://www.nature.com/articles/d42473-019-00271-9;

https://www.nature.com/articles/s41684-019-0367-x

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. PMID: 28835507

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. PMID: 26019217

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. PMID: 25739762

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. PMID: 24106222

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. PMID: 23043073

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. PMID: 21857672

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. PMID: 21520180

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. PMID: 19794140

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. PMID: 18026085

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. PMID: 17726165

Review Articles

Cantore A, Naldini L. WFH State-of-the-art paper 2020: In vivo lentiviral vector gene therapy for haemophilia. Haemophilia. 2020 Jun 14. PMID: 32537776

Ciccocioppo R, Cantore A, Chaimov D, Orlando G. Regenerative medicine: the red planet for clinicians. Intern Emerg Med. 2019 Jun 15. PMID: 31203564

Annoni A, Gregori S, Naldini L, Cantore A. Modulation of immune responses in lentiviral vector-mediated gene transfer. Cell Immunol. 2018. PMID: 29735164

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