Virotherapy and immunotherapy Lab


Ramon Alemany- Group Leader
Rafael Moreno - Postdoc
Ahmed Al Zaher  - PhD candidate
Carlos Fajardo - PhD student
Marcel Arias - PhD student
Jana de Sostoa - PhD student
Luis Rojas - PhD student
Silvia Torres - Lab technician
Dolores Ramos - Lab technician
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Ramon Alemany is Doctor in Biology/Genetics by the University of Barcelona, Spain. In 1993 he began working on adenoviruses for cancer gene therapy as a postdoct at the MD, Anderson Cancer Center, Houston, TX. His research on adenoviral vectors and oncolytic adenoviruses applied to cancer therapy continued in Baxter Healthcare, Round Lake, IL, and later at the University of Alabama in Birmingham, AL. In 2001 he returned to Barcelona to lead a research a group on cancer virotherapy at the Catalan Institute of Oncology-IDIBELL, which is now part of the ProCure Program. He has published more than 100 original articles and 14  patents on the therapeutic use of adenovirus against cancer. In 2009 he co-founded VCN Biosciences.
  1. Fajardo CA, Guedan S, Rojas LA, Moreno R, Arias-Badia M, de Sostoa J, June CH, Alemany R. Oncolytic adenoviral delivery of an EGFR-targeting T cell engager improves antitumor efficacy.Cancer Res. 2017 Jan 31. pii: canres.1708.2016. doi: 10.1158/0008-5472.CAN-16-1708. [Epub ahead of print]. PMID:28143835
  2. Mato-Berciano A, Raimondi G, Maliandi MV, Alemany R, Montoliu L, Fillat C. A NOTCH-sensitive uPAR-regulated oncolytic adenovirus effectively suppresses pancreatic tumor growth and triggers synergistic anticancer effects with gemcitabine and nab-paclitaxel. Oncotarget. 2017 Feb 7. doi: 10.18632/oncotarget.15169. [Epub ahead of print] PMID:28186974
  3. Eriksson E, Moreno R, Milenova I, Liljenfeldt L, Dieterich LC, Christiansson L, Karlsson H, Ullenhag G, Mangsbo SM, Dimberg A, Alemany R, Loskog A. Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment. Gene Ther. 2017
  4. Rojas LA, Moreno R., Calderón H., Alemany R. Adenovirus CAR-mediated binding to human erythrocytes does not preclude systemic transduction. Gene Therapy. 2016
  5. Rojas LA, Condezo GN, Moreno R, Fajardo CA, Arias-Badia M, San Martín C, Alemany  R.Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery.J Control Release. 2016. 237:78-88
  6. Melen GJ, Franco-Luzón L, Ruano D, González-Murillo Á, Alfranca A, Casco F, Lassaletta Á, Alonso M, Madero L, Alemany R,García-Castro J, Ramírez M. Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells. Cancer Lett. 2016 Feb 28;371(2):161-70.
  7. Sanz-Pamplona R, Gil-Hoyos R, López-Doriga A, Alonso MH, Aussó S, Molleví DG, Santos C, Sanjuán X, Salazar R, Alemany R, Moreno V. .Mutanome and expression of immune response genes in microsatelite stable colon cancer. Oncotarget 2016. Feb 9. doi: 10.18632/oncotarget.7293
  8. Alemany R, Izeta A, Garcia-Sancho J.Highlights of 8th Biennial Congress of the Spanish Society of Gene and Cell Therapy. Hum Gene Ther. 2016 Jan;27(1):92-3
  9. Vera B, Martínez-Vélez N, Xipell E, de la Rocha A, Patiño A, Castresana JS, Gonzalez-Huarriz M, Cascallo M, Alemany R, Alonso MM. Characterization of the antiglioma effect of the oncolytic adenovirus VCN-01. PLoS One. 2016 Jan 25;11(1):e0147211
  10. Martínez-Vélez N, Xipell E, Vera B, Acanda de la Rocha A, Zalacain M, Marrodan L, Gonzalez-Huarriz M, Toledo G, Cascallo M, Alemany R, Patiño-García A, Alonso MM. The oncolytic adenovirus VCN-01 as therapeutic approach against pediatric osteosarcoma. Clin Cancer Res. 2016 May 1;22(9):2217-25
  11. Zaiss AK, Foley EM, Lawrence R, Schneider LS, Hoveida H, Secrest P, Catapang AB, Yamaguchi Y,Alemany R, Shayakhmetov DM, Esko JD, Herschman HR. Hepatocyte Heparan Sulfate is Required for Adeno-Associated Virus 2 but Dispensable for Adenovirus 5 Liver Transduction In Vivo. J Virol. 2015 Oct 21;90(1):412-20
  12. Rodríguez-García A, Svensson E, Gil-Hoyos R, Fajardo CA, Rojas LA, Arias-Badia M, Loskog  AS, Alemany R. Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity. Gene Ther. 22(7):596-601. 2015.
  13. Rodriguez-Garcia A, Gimenez-Alejandre M, Rojas J, Moreno R, Bazan-Peregino M, Cascallo M, Alemany R.  Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG-binding domain replacement with RGD and hyaluronidase expression. Clin Cancer Res. 21(6):1406-18. 2015
  14. Hoyos, V; Del Bufalo, F; Yagyu, S; Ando, M; Dotti, G; Suzuki, M; Bouchier-Hayes, L; Alemany, R; Brenner, MK. Mesenchymal Stromal Cells for Linked Delivery of Oncolytic and Apoptotic Adenoviruses to Non-small-cell Lung Cancers. Molecular Therapy 23(9): 1497-1506 If: 6.227. 2015. (Q1,D1)
  15. Agirre M, Zarate J, Ojeda E, Puras G, Rojas LA, Alemany R, Pedraz JL. Delivery of an adenovirus vector plasmid by ultrapure oligochitosan based polyplexes. Int J Pharm. 479(2):312-9.  2015
  16. Martinez-Quintanilla J, He D, Wakimoto H, Alemany R, Shah K. Encapsulated stem cells loaded with hyaluronidase-expressing oncolytic virus for brain tumor therapy. Mol  Ther. 23(1):108-18. 2015.
  17. Dong W, van Ginkel JW, Au KY, Alemany R, Meulenberg JJ, van Beusechem VW. ORCA-010, a Novel Potency-Enhanced Oncolytic Adenovirus, Exerts Strong Antitumor Activity in Preclinical Models. Hum Gene Ther. 25(10):897-904. 2014
  18. Puig-Saus C, Rojas LA, Laborda E, Figueras A, Alba R, Fillat C, Alemany R. iRGD tumor-penetrating peptide-modified oncolytic adenovirus shows enhanced tumor transduction, intratumoral dissemination and antitumor efficacy. Gene Ther.  21: 767-774. 2014
  19. José A, Rovira-Rigau M, Luna J, Giménez-Alejandre M, Vaquero E, de la Torre BG, Andreu D, Alemany R, Fillat C. A genetic fiber modification to achieve matrix-metalloprotease-activated infectivity of oncolytic adenovirus. J Control Release.  Jul 15. pii: S0168-3659(14)00479-9. doi: 10.1016. 2014
  20. Lopez Gordo E, Podgorski II, Downes NL, Alemany R. Circumventing anti-vector immunity: Potential use of non-human adenoviral vectors. Hum Gene Ther. 2014. 25(4):285-300. 2014
  21. Majhen D, Calderon H, Chandra N, Fajardo CA, Rajan A, Alemany R, Custers J.  Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field. Hum Gene Ther. 25(4):301-17. 2014
  22. Laborda E, Puig-Saus C, Rodriguez-García A, Moreno R, Cascalló M, Pastor J, Alemany R.A pRb-responsive, RGD-modified, and hyaluronidase-armed canine oncolytic adenovirus for application in veterinary oncology. Mol Ther. 22(5):986-98. 2014
  23. Puig-Saus C, Laborda E, Rodríguez-García A, Cascalló M, Moreno R, Alemany R. The combination of i-leader truncation and gemcitabine improves oncolytic adenovirus efficacy in an immunocompetent model. Cancer Gene Ther.  21(2):68-73. 2014
  24. Gil-Hoyos R, Miguel-Camacho J, Alemany R. Oncolytic adenovirus characterization: activity and immune responses. Methods Mol Biol. 1089:117-32. 2014
  25. Laborda E, Puig-Saus C, Cascalló M, Chillón M, Alemany R.Adeno-Associated Virus Enhances Wild-Type and Oncolytic Adenovirus Spread. Hum Gene Ther Methods. 24(6):372-80. 2013.
  26. José A, Sobrevals L, Miguel Camacho-Sánchez J, Huch M, Andreu N, Ayuso E, Navarro P, Alemany R, Fillat C. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts. Oncotarget. 4(1):94-105. 2013.
  27. Alemany R. Viruses in cancer treatment. Clin Transl Oncol. 15(3):182-8. 2013.
  28. Alemany R. Chapter four--Design of improved oncolytic adenoviruses. Adv Cancer Res. 115:93-114. Review. 2012.
  29. Coughlan L, Vallath S, Gros A, Giménez-Alejandre M, Van Rooijen N, Thomas GJ, Baker AH, Cascalló M, Alemany R, Hart IR. Combined fiber modifications both to target α(v)β(6) and detarget the coxsackievirus-adenovirus receptor improve virus toxicity profiles in vivo but fail to improve antitumoral efficacy relative to adenovirus serotype 5. Hum Gene Ther. 23(9):960-79. 2012.
  30. Guedan S, Grases D, Rojas JJ, Gros A, Vilardell F, Vile R, Mercade E, Cascallo M, Alemany R. GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution. Gene Ther. 19(11):1048-57. 2012.
  31. Koski A, Raki M, Nokisalmi P, Liikanen I, Kangasniemi L, Joensuu T, Kanerva A, Pesonen S, Alemany R, Hemminki A. Verapamil Results in Increased Blood Levels of Oncolytic Adenovirus in Treatment of Patients With Advanced Cancer. Mol Ther. 20 (1) , 221-229. 2012.
  32. Giménez-Alejandre M, Gros A, Alemany R. Construction of capsid-modified adenoviruses by recombination in yeast and purification by iodixanol-gradient. Methods Mol Biol. 797:21-34. 2012.
  33. Puig-Saus C, Gros A, Alemany R, Cascalló M. Adenovirus i-Leader Truncation Bioselected Against Cancer-associated Fibroblasts to Overcome Tumor Stromal Barriers. Mol. Ther. 20(1):54-62. 2012.
  34. Rojas JJ, Gimenez-Alejandre M, Gil-Hoyos R, Cascallo M, Alemany R. Improved systemic antitumor therapy with oncolytic adenoviruses by replacing the fiber shaft HSG-binding domain with RGD. Gene Ther. 19(4):453-7. 2012.
  35. Abate-Daga D, Andreu N, Camacho-Sánchez J, Alemany R, Herance R, Millán O, Fillat C. Oncolytic Adenoviruses Armed with Thymidine Kinase Can Be Traced by PET Imaging and Show Potent Antitumoural Effects by Ganciclovir Dosing.. PLoS One. 6(10):e26142. 2011.
  36. Chillon M, Alemany R. Methods to construct adenovirus vectors. Methods Mol Biol. 737:117-38. 2011.
  37. Rojas JJ, Guedan S, Searle PF, Martinez-Quintanilla J, Gil-Hoyos R, Alcayaga-Miranda F, Cascallo M, Alemany R.Minimal RB-responsive E1A Promoter Modification to Attain Potency, Selectivity, and Transgene-arming Capacity in Oncolytic Adenoviruses. Mol Ther. 18:1960-71.2010.
  38. Alcayaga-Miranda F, Cascallo M, Rojas JJ, Pastor J, Alemany R. Osteosarcoma cells as carriers to allow antitumor activity of canine oncolytic adenovirus in the presence of neutralizing antibodies. Cancer Gene Ther. 17(11):792-802. 2010.
  39. Ramírez M, García-Castro J, Alemany R. Oncolytic virotherapy for neuroblastoma. Discov Med. 10(54):387-93. 2010.
  40. Nokisalmi P, Pesonen S, Escutenaire S, Särkioja M, Raki M, Cerullo V, Laasonen L, Alemany R, Rojas J, Cascallo M, Guse K, Rajecki M, Kangasniemi L, Haavisto E, Karioja-Kallio A, Hannuksela P, Oksanen M, Kanerva A, Joensuu T, Ahtiainen L, Hemminki AOncolytic adenovirus ICOVIR-7 in patients with advanced and refractory solid tumors. Clin Cancer Res. 16(11):3035-43. 2010.
  41. Guedan S, Rojas JJ, Gros A, Mercade E, Cascallo M, Alemany R. Hyaluronidase Expression by an Oncolytic Adenovirus Enhances Its Intratumoral Spread and Suppresses Tumor Growth. Mol Ther. 18(7):1275-83. 2010.
  42. Urruticoechea A, Alemany R, Balart J, Villanueva A, Viñals F, Capellá G Recent advances in cancer therapy: an overview. Curr Pharm Des. 16(1):3-10. 2010.
  43. Gros A, Puig C, Guedan S, Rojas J.J., Alemany R, Cascallo M. Verapamil enhances the antitumoral activity of oncolytic adenoviruses. Molecular Ther. 18(5):903-11. 2010.
  44. Garcia-Castro J., Alemany R., Cascallo M., Martínez-Quintanilla J., Arriero MM., Lassaletta A., Madero L., Ramírez M., Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study. Cancer Gene Ther. 17(7):476-83. 2010.
Recent projects:
 
Title: Adenonet (BIO2015-68990)(http://wwwuser.cnb.csic.es/~adenonet)
Funding Agency: REDT from the Ministerio de Economía y Competitividad (Mineco). Participant. 2016-2019.
Assigned budget for networking activities.
 
Title: Motricolor Grant Agreement 635342.
Funding Agency: European Union Horizon 2020 Research and Innovation Program.
Period: 2016-2020.
Assigned budget of 90.000€.
 
Title: Cure4RB Project Grant.
Funding Agency: Retos Colaboration RTC-2015-4319-1 from the Minesterio de Economía y Competitividad (Mineco).
Period: 2015-2019.
Assigned budget of 80.000 €.
 
Title: ABORDAGE DE ASPECTOS CLAVE EN LA VIROTERAPIA DEL CANCER CON ADENOVIRUS: LLEGADA
DE VIRUS SISTEMICO A TUMORES, REPLICACION, DISEMINACION, E INMUNIDAD (Ref BIO2014-57716-C2-1-R)
Funding Agency: Plan Nacional de I+D+i. Ministerio de Economía y Competitividad. IP Coordinador.
PI: Ramon Alemany. (Nº participating centers: 2; IDIBAPS, IDIBELL).
Period: 2014-2017.
Budget: 225.000euros     
Cristina Fillat, IDIBAPS, Barcelona.
Angel Montero, Hospital St. Joan Deu, Barcelona.
Josep Pastor, Universitat Autònoma de Barcelona.
Alena Gros, Instituto de Oncología Vall Hebron, Barcelona.  
Josep Maria Piulats, ICO, L´Hospitalet de Llobregat.
Rebeca Sanz, ICO, L´Hospitalet de Llobregat.
Ramon Salazar, ICO, L´Hospitalet de Llobregat.
Manel Cascalló, VCN Biosciences, St. Cugat del Vallés.
Javier García Castro, ISCIII, Madrid.
Daniel Lopez Rodriguez, ISCIII, Madrid.
Manuel Ramírez Orellana, Hospital Niño Jesús, Madrid.
Francisco Javier Lacadena, Universidad Complutense de Madrid.
Carmen SanMartin, CNB, Madrid.
Pilar Martin Duque, Instituto Aragonés de la Salud, Zaragoza.
Rafael Sanjuan, Universidad de Valencia.
Sonia Guedan, University of Pennsylvania.
To inquiere about open positivas please contact:

​Dr. Ramon Alemany
Program Against Cancer Therapeutic Resistance, ProCURE
Catalan Institute of Oncology
Bellvitge Biomedical Research Institute, IDIBELL
3 floor, LRT1, Hospital Duran i Reynals
Gran Via 199-203, 08907 L’Hospitalet de Llobregat