Ignacio Melero

Summary

Affiliation: University of Navarra
Country: Spain

Publications

  1. doi request reprint Multi-layered action mechanisms of CD137 (4-1BB)-targeted immunotherapies
    Ignacio Melero
    Center for Applied Medical Research, Universidad de Navarra, Avenida de Pio XII, 55 31008 Pamplona, Spain
    Trends Pharmacol Sci 29:383-90. 2008
  2. ncbi request reprint Making the Most of Cancer Surgery with Neoadjuvant Immunotherapy
    Ignacio Melero
    University Clinic, University of Navarra and Instituto de Investigacion Sanitaria de Navarra IdISNA, Pamplona, Spain
    Cancer Discov 6:1312-1314. 2016
  3. doi request reprint Virotherapy with a Semliki Forest Virus-Based Vector Encoding IL12 Synergizes with PD-1/PD-L1 Blockade
    Jose I Quetglas
    Division of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, and University Clinic, University of Navarra, Pamplona, Navarra, Spain
    Cancer Immunol Res 3:449-54. 2015
  4. doi request reprint Strict requirement for vector-induced type I interferon in efficacious antitumor responses to virally encoded IL12
    Ignacio Melero
    Center for Applied Medical Research CIMA and Clínica Universidad de Navarra, University of Navarra, Navarra, Spain
    Cancer Res 75:497-507. 2015
  5. pmc Routing cancer immunology and immunotherapy from the lab to the clinic 4-5 th March 2014, Center for Applied Medical Research and University Clinic, Pamplona, Spain
    M Angela Aznar
    Center for Applied Medical Research, CIMA and University Clinic, University of Navarra, Pamplona, Spain
    J Transl Med 12:202. 2014
  6. pmc Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes
    C Alfaro
    Gene Therapy and Hepatology Division, CIMA, Universidad de Navarra, Pamplona, Spain
    Br J Cancer 100:1111-9. 2009
  7. pmc Cardiotrophin-1 determines liver engraftment of syngenic colon carcinoma cells through an immune system-mediated mechanism
    Matilde Bustos
    Gene Therapy and Hepatology Unit Center for Applied Medical Research University Clinic of Navarra Pamplona, Spain
    Oncoimmunology 1:1527-1536. 2012
  8. pmc SimB16: modeling induced immune system response against B16-melanoma
    Francesco Pappalardo
    University of Catania, Catania, Italy
    PLoS ONE 6:e26523. 2011
  9. ncbi request reprint [Specialized dendritic cells in cross-presentation of exogenous antigens to cytotoxic T lymphocytes]
    C Alfaro
    Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Pamplona, 31008, Spain
    An Sist Sanit Navar 36:519-37. 2013
  10. doi request reprint Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination
    Ignacio Melero
    Department of Oncology, Centro de Investigación Médica Aplicada, Clinica Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 19:997-1008. 2013

Detail Information

Publications89

  1. doi request reprint Multi-layered action mechanisms of CD137 (4-1BB)-targeted immunotherapies
    Ignacio Melero
    Center for Applied Medical Research, Universidad de Navarra, Avenida de Pio XII, 55 31008 Pamplona, Spain
    Trends Pharmacol Sci 29:383-90. 2008
    ....
  2. ncbi request reprint Making the Most of Cancer Surgery with Neoadjuvant Immunotherapy
    Ignacio Melero
    University Clinic, University of Navarra and Instituto de Investigacion Sanitaria de Navarra IdISNA, Pamplona, Spain
    Cancer Discov 6:1312-1314. 2016
    ..Cancer Discov; 6(12); 1312-4. ©2016 AACRSee related article by Liu and colleagues, p. 1382...
  3. doi request reprint Virotherapy with a Semliki Forest Virus-Based Vector Encoding IL12 Synergizes with PD-1/PD-L1 Blockade
    Jose I Quetglas
    Division of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, and University Clinic, University of Navarra, Pamplona, Navarra, Spain
    Cancer Immunol Res 3:449-54. 2015
    ..PD-L1-mediated adaptive resistance thereby provides a mechanistic explanation of the observed synergistic effects achieved by the SFV-IL12 + anti-PD-1 mAb combination...
  4. doi request reprint Strict requirement for vector-induced type I interferon in efficacious antitumor responses to virally encoded IL12
    Ignacio Melero
    Center for Applied Medical Research CIMA and Clínica Universidad de Navarra, University of Navarra, Navarra, Spain
    Cancer Res 75:497-507. 2015
    ....
  5. pmc Routing cancer immunology and immunotherapy from the lab to the clinic 4-5 th March 2014, Center for Applied Medical Research and University Clinic, Pamplona, Spain
    M Angela Aznar
    Center for Applied Medical Research, CIMA and University Clinic, University of Navarra, Pamplona, Spain
    J Transl Med 12:202. 2014
    ..Promising agents to target cancer cells and therapeutic approaches that are under translation from bench to patients were presented. ..
  6. pmc Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes
    C Alfaro
    Gene Therapy and Hepatology Division, CIMA, Universidad de Navarra, Pamplona, Spain
    Br J Cancer 100:1111-9. 2009
    ..These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators...
  7. pmc Cardiotrophin-1 determines liver engraftment of syngenic colon carcinoma cells through an immune system-mediated mechanism
    Matilde Bustos
    Gene Therapy and Hepatology Unit Center for Applied Medical Research University Clinic of Navarra Pamplona, Spain
    Oncoimmunology 1:1527-1536. 2012
    ..These findings demonstrate that the seed and soil concept to understand metastasis can be locally influenced by cytokines as well as by the cellular immune system...
  8. pmc SimB16: modeling induced immune system response against B16-melanoma
    Francesco Pappalardo
    University of Catania, Catania, Italy
    PLoS ONE 6:e26523. 2011
    ..The biologically oriented in silico model derived in this work will be used to predict treatment failure or success in other pre-clinical conditions eventually leading new promising in vivo experiments...
  9. ncbi request reprint [Specialized dendritic cells in cross-presentation of exogenous antigens to cytotoxic T lymphocytes]
    C Alfaro
    Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Pamplona, 31008, Spain
    An Sist Sanit Navar 36:519-37. 2013
    ..In vivo targeting of antigens with monoclonal antibodies against DEC-205 or CLEC9A attains very robust immune responses and is a strategy undergoing clinical trials for chronic viral diseases and malignancies. ..
  10. doi request reprint Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination
    Ignacio Melero
    Department of Oncology, Centro de Investigación Médica Aplicada, Clinica Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 19:997-1008. 2013
    ..Combinations with other more conventional means of treatment such as radiotherapy, chemotherapy, or cancer vaccines also hold much promise...
  11. pmc Agonist antibodies to TNFR molecules that costimulate T and NK cells
    Ignacio Melero
    Centro de Investigación Médica Aplicada, and Clinica Universidad de Navarra, Pamplona, Navarra, Spain
    Clin Cancer Res 19:1044-53. 2013
    ..Combinations with other immunomodulatory mAb that block T-cell checkpoint blockade receptors such as CTLA-4 and PD-1 are also promising...
  12. pmc Defining the critical hurdles in cancer immunotherapy
    Bernard A Fox
    Earle A, Chiles Research Institute, Robert W, Franz Research Center, Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA
    J Transl Med 9:214. 2011
    ..Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer...
  13. pmc Palettes of vaccines and immunostimulatory monoclonal antibodies for combination
    Ignacio Melero
    Gene Therapy Unit, Centro de Investigación Médica Aplicada CIMA, Clinica Universitaria, Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 15:1507-9. 2009
    ..e., CTLA-4, PD-1). These powerful agents can be guided by cancer vaccines to enhance immunity against tumor but not self tissues. Clinically powerful therapeutic synergies are at hand...
  14. ncbi request reprint Immunogenic cell death and cross-priming are reaching the clinical immunotherapy arena
    Ignacio Melero
    Centro de Investigación Médica Aplicada, Clinica Universitaria and School of Medicine, University of Navarra, Pamplona, Spain
    Clin Cancer Res 12:2385-9. 2006
  15. ncbi request reprint The many sounds of T lymphocyte silence
    Ignacio Melero
    Department of Medicine, CIMA and Clinica Universitaria, University of Navarra, Pamplona, Spain
    Immunol Res 33:135-47. 2005
    ..Recognition of a specific antigen is therefore shaped and tuned by co-stimulatory and co-inhibitory receptor-ligand pairs. At last, immunologists are beginning to exploit the rules governing these assorted sounds of T cell silence...
  16. ncbi request reprint Immunostimulatory monoclonal antibodies for cancer therapy
    Ignacio Melero
    Centro de Investigación Médica Aplicada CIMA and Clínica Universitaria, Universidad de Navarra, Pamplona, Spain
    Nat Rev Cancer 7:95-106. 2007
    ..Importantly, mAbs of this type have now entered clinical trials with encouraging initial results...
  17. doi request reprint Clinical development of combination strategies in immunotherapy: are we ready for more than one investigational product in an early clinical trial?
    Jose L Perez-Gracia
    Centro de Investigación Médica Aplicada y Clinica Universitaria Universidad de Navarra, Avenida de Pio XII 55, 31008 Pamplona, Spain
    Immunotherapy 1:845-53. 2009
    ..Such 'short-cut' combination immunotherapy trials can bring much needed efficacy earlier to the bedside...
  18. ncbi request reprint Anti-ICAM-2 monoclonal antibody synergizes with intratumor gene transfer of interleukin-12 inhibiting activation-induced T-cell death
    Ignacio Melero
    Centro de Investigación Médica Aplicada CIMA, Facultad de Medicina, Gene Therapy Unit, Universidad de Navarra, 31008 Pamplona, Spain
    Clin Cancer Res 9:3546-54. 2003
    ..We sought to design combined therapy strategies with AdCMVIL-12 plus anti-ICAM-2 mAbs and to identify their mechanism of action...
  19. ncbi request reprint An anti-ICAM-2 (CD102) monoclonal antibody induces immune-mediated regressions of transplanted ICAM-2-negative colon carcinomas
    Ignacio Melero
    Gene Therapy Unit, Department of Medicine, University of Navarra School of Medicine, C Irunlarrea, I 31008 Pamplona, Spain
    Cancer Res 62:3167-74. 2002
    ....
  20. doi request reprint Intratumoral injection of interferon-α and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy
    Juan Dubrot
    CIMA and Clinica Universitaria, Universidad de Navarra, Pamplona, Spain
    Int J Cancer 128:105-18. 2011
    ..The described strategy is realistic because (i) agents of each kind are clinically available and (ii) equivalent procedures in humans are feasible...
  21. ncbi request reprint The combined actions of NK and T lymphocytes are necessary to reject an EGFP+ mesenchymal tumor through mechanisms dependent on NKG2D and IFN gamma
    Ainhoa Arina
    Gene Therapy Unit, Centro de Investigación Médica Aplicada, University of Navarra, Pamplona, Spain
    Int J Cancer 121:1282-95. 2007
    ..Therefore, complete rejection of these mesenchymal tumors requires a concerted set of activities including direct tumor-cell destruction and IFN gamma production that are mediated by both NK and T cells...
  22. doi request reprint Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ
    Juan Dubrot
    Centro de Investigación Médica Aplicada, Universidad de Navarra, Av Pio XII, 55, 31008, Pamplona, Spain
    Cancer Immunol Immunother 59:1223-33. 2010
    ..This study characterizes the liver infiltrates and the target dependency of the phenomena and addresses the question of whether tumors nested in the liver are a more favorable target for CD137-based immunotherapy...
  23. ncbi request reprint Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas
    Guillermo Mazzolini
    Division of Hepatology and Gene Therapy, Department of Radiology, Clinica Universitaria School of Medicine, University of Navarra, C Irunlarrea, S N, 31008 Pamplona, Spain
    J Clin Oncol 23:999-1010. 2005
    ..Secondarily, we have evaluated biologic effects and antitumoral activity...
  24. doi request reprint In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb
    Oihana Murillo
    Gene Therapy Unit, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Spain
    Eur J Immunol 39:2424-36. 2009
    ....
  25. pmc Intensive pharmacological immunosuppression allows for repetitive liver gene transfer with recombinant adenovirus in nonhuman primates
    Antonio Fontanellas
    Gene Therapy and Hepatology Area, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain
    Mol Ther 18:754-65. 2010
    ..This strategy allows measurable gene retransfer to the liver as late as 15 months following the first adenoviral exposure in a macaque, which has undergone a total of four treatments with the same adenoviral vector...
  26. ncbi request reprint CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination
    Noelia Casares
    Department of Internal Medicine, Medical School, University Clinic and Fundación para la Investigación Médica Aplicada, University of Navarra, Pamplona, Spain
    J Immunol 171:5931-9. 2003
    ....
  27. ncbi request reprint Potentiation of therapeutic immune responses against malignancies with monoclonal antibodies
    Oihana Murillo
    Centro de Investigación Médica Aplicada and Clinica Universitaria, Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 9:5454-64. 2003
    ..This new group of antitumor agents holds promise for at least additive effects with conventional therapies of cancer and deserves intensive translational research...
  28. ncbi request reprint Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus
    Laura Arribillaga
    Division of Hepatology and Gene Therapy, University Clinic, Faculty of Medicine, Center for Applied Medical Research CIMA, University of Navarra, Pio XII 55, 31008 Pamplona, Spain
    Vaccine 23:3493-9. 2005
    ..Thus, combination of immunostimulatory anti-CD137 mAb with recombinant adenoviruses expressing HCV proteins might be useful in strategies of immunization against HCV...
  29. doi request reprint Delivery of immunostimulatory monoclonal antibodies by encapsulated hybridoma cells
    Juan Dubrot
    Centro de Investigación Médica Aplicada CIMA, University of Navarra, Pamplona, Spain
    Cancer Immunol Immunother 59:1621-31. 2010
    ..This form of administration permitted combinations of more than one immunostimulatory monoclonal antibody to exploit the synergistic effects such as those known to be displayed by anti-CD137 and anti-OX40 mAb...
  30. ncbi request reprint Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer
    Ainhoa Arina
    University of Navarra, Centro de Investigación Médica Aplicada and Clinica Universitaria, Gene Therapy Unit, Avda Pio XII 55, 31008, Pamplona, Spain
    Expert Opin Biol Ther 7:599-615. 2007
    ..However, there is plenty of opportunity for targeted intervention of inhibitory/activatory surface receptors and for adoptive cell therapy with autologous or allogeneic NK cells...
  31. ncbi request reprint Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8
    Esperanza Feijoo
    Division of Hepatology and Gene Therapy, Clinica Universitaria School of Medicine, Foundation for Applied Medical Research, Universidad de Navarra, Pamplona, Spain
    Int J Cancer 116:275-81. 2005
    ..Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion...
  32. pmc Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation
    Carlos Alfaro
    Gene Therapy and Hepatology Division, Centro de Investigación Médica Aplicada, Pamplona, Spain
    PLoS ONE 6:e17922. 2011
    ..Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogenesis promotion...
  33. pmc Therapeutic antitumor efficacy of anti-CD137 agonistic monoclonal antibody in mouse models of myeloma
    Oihana Murillo
    Gene Therapy Unit, Centro de Investigación Médica Aplicada, Pamplona, Spain
    Clin Cancer Res 14:6895-906. 2008
    ..This study explores anti-CD137 mAbs for multiple myeloma treatment in preclinical models of the disease because they safely augment tumor immunity and are in clinical trials for other cancers...
  34. doi request reprint Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels
    Alvaro Teijeira
    Department of Oncology, Center for Applied Medical Research, Pamplona, Spain
    J Invest Dermatol 133:2276-85. 2013
    ..Therefore, under inflammatory conditions, integrin ligands form three-dimensional membrane projections around DCs. These structures offer docking sites for DC transit from the tissue toward the lymphatic vessel lumen. ..
  35. doi request reprint Antitumor immunotherapeutic and toxic properties of an HDL-conjugated chimeric IL-15 fusion protein
    Maria C Ochoa
    Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    Cancer Res 73:139-49. 2013
    ..Sushi-IL-15-Apo as a recombinant protein was also bioactive in vivo, became conjugated to HDL, and displayed immunotherapeutic effects against metastatic disease...
  36. doi request reprint The HIF-1α hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy
    Asis Palazon
    CIMA and CUN University of Navarra, Pamplona, Navarra, Spain
    Cancer Discov 2:608-23. 2012
    ..As a result, low-dose intratumoral injections avoid liver inflammation, achieve antitumor systemic effects, and permit synergistic therapeutic effects with PD-L1/B7-H1 blockade...
  37. ncbi request reprint Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12
    Mercedes Rodriguez-Calvillo
    Gene Therapy Unit, Department of Internal Medicine, University of Navarra, Pamplona, Spain
    Exp Hematol 30:195-204. 2002
    ..The aim of this work was to study the possible involvement of natural killer (NK) cells in this setting...
  38. pmc Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes
    Carlos Alfaro
    Gene Therapy Unit, CIMA, Universidad de Navarra, Pamplona, Spain
    PLoS ONE 6:e29300. 2011
    ..In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC...
  39. ncbi request reprint Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication
    Eduardo Huarte
    Center for Applied Medical Research, School of Medicine, and University Clinic, University of Navarra, Avenida Pio XII, 55, 31008 Pamplona, Spain
    Mol Ther 14:129-38. 2006
    ..However, type I IFN might modulate antitumor and antiadenoviral immune responses and thus influence the outcome of gene immunotherapy...
  40. pmc Liver gene transfer of interkeukin-15 constructs that become part of circulating high density lipoproteins for immunotherapy
    Maria C Ochoa
    Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    PLoS ONE 7:e52370. 2012
    ..The improved pharmacokinetic profile and the strong biological activity of APO-IL-15 fusion protein holds promise for further development in combination with other immunotherapies...
  41. pmc Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates
    Carmen Unzu
    Gene Therapy and Hepatology Area, Centre for Applied Medical Research CIMA, University of Navarra, Navarra, Spain
    J Transl Med 10:122. 2012
    ....
  42. ncbi request reprint Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma
    Iñigo Tirapu
    Gene Therapy Unit, Department of Medicine, Centro de Investigación Médica Aplicada and Clinica Universitaria, University of Navarra School of Medicine, Pamplona, Spain
    Cancer Res 66:2442-50. 2006
    ..Our findings are similar with the inhibitory role described for the dim CD80 expression on immature dendritic cells, providing an explanation for the low levels of CD80 expression described in various human malignancies...
  43. doi request reprint Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN-α
    Ana Rouzaut
    Center for Applied Medical Research, School of Medicine, University of Navarra, Pamplona, Spain
    Eur J Immunol 40:3054-63. 2010
    ..Collectively, these results indicate a role for type I IFN in directing DC toward LN under inflammatory conditions...
  44. doi request reprint Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients
    Carlos Alfaro
    Gene Therapy and Hepatology Unit, Center for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain
    J Immunol 187:6130-42. 2011
    ..This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing...
  45. doi request reprint Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2-/-IL2Rγnull Immunodeficient Mice
    Miguel F Sanmamed
    Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain Centro de Investigación Médica Aplicada CIMA, Universidad de Navarra, Pamplona, Spain
    Cancer Res 75:3466-78. 2015
    ..Our results offer a proof of concept for the use of humanized mouse models for surrogate efficacy and histology investigations of immune checkpoint drugs and their combinations...
  46. pmc Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12
    Jose I Quetglas
    Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Navarra, Spain
    Mol Ther 20:1664-75. 2012
    ..This efficacious combinatorial immunotherapy strategy offers feasibility for clinical translation since anti-CD137 mAbs are already undergoing clinical trials and development of clinical-grade SFV-IL-12 vectors is in progress...
  47. doi request reprint T cell costimulation with anti-CD137 monoclonal antibodies is mediated by K63-polyubiquitin-dependent signals from endosomes
    Ivan Martinez-Forero
    Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona 31008, Spain
    J Immunol 190:6694-706. 2013
    ..As a whole, these findings advance our knowledge of the mechanisms of action of anti-CD137 immunostimulatory mAbs such as those currently undergoing clinical trials in cancer patients...
  48. ncbi request reprint Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells
    Maria Vera
    Division of Hepatology and Gene Therapy, CIMA, School of Medicine, University of Navarra, Pio XII 55, 31008 Pamplona, Spain
    Mol Ther 12:950-9. 2005
    ....
  49. ncbi request reprint CD8 T cell priming in the presence of IFN-α renders CTLs with improved responsiveness to homeostatic cytokines and recall antigens: important traits for adoptive T cell therapy
    Sandra Hervas-Stubbs
    Division of Gene Therapy and Hepatology, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
    J Immunol 189:3299-310. 2012
    ..Therefore, exposure to IFN-α during priming of naive CD8 T cells imprints decisive information on the expanded cells that can be exploited to improve the efficacy of adoptive T cell therapy...
  50. doi request reprint Synergistic effects of CTLA-4 blockade with tremelimumab and elimination of regulatory T lymphocytes in vitro and in vivo
    Natalia Suarez
    Biochemistry Department, Clinica Universidad de Navarra, Pamplona, Spain
    Int J Cancer 129:374-86. 2011
    ..Taken together, these experiments indicate that tremelimumab therapy may benefit from previous or concomitant T(reg) depletion...
  51. ncbi request reprint Clinical implications of antigen transfer mechanisms from malignant to dendritic cells. exploiting cross-priming
    Ainhoa Arina
    Centro de Investigación Médica Aplicada CIMA, School of Medicine and Cell Therapy Area Clínica Universitaria, University of Navarra, Pamplona, Spain
    Exp Hematol 30:1355-64. 2002
    ..Artificial enhancement of tumor antigen cross-presentation and control of the immune-promoting status of the antigen-presenting DC will have important therapeutic implications in the near future...
  52. doi request reprint Effects of IFN-α as a signal-3 cytokine on human naïve and antigen-experienced CD8(+) T cells
    Sandra Hervas-Stubbs
    Division of Gene Therapy and Hepatology, Centre for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain
    Eur J Immunol 40:3389-402. 2010
    ..Our findings in human CD8(+) T cells are informative to understand and improve IFN-α-based therapies for viral and malignant diseases...
  53. ncbi request reprint Effective tumor immunotherapy: start the engine, release the brakes, step on the gas pedal,...and get ready to face autoimmunity
    Iñigo Tirapu
    Gene Therapy Division, Facultad de Medicina and Clinica Universitaria, Universidad de Navarra, Pamplona, Spain
    Arch Immunol Ther Exp (Warsz) 50:13-8. 2002
    ....
  54. ncbi request reprint Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming
    Maria E Rodriguez-Ruiz
    Division of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra and Instituto de Investigacion Sanitaria de Navarra IdISNA, Pamplona, Spain University Clinic, University of Navarra and Instituto de Investigacion Sanitaria de Navarra IdISNA, Pamplona, Spain
    Cancer Res 76:5994-6005. 2016
    ..Cancer Res; 76(20); 5994-6005. ©2016 AACR...
  55. ncbi request reprint Biologic therapy of liver tumors
    Jesus Prieto
    Division of Hepatology and Gene Therapy, Fundación para la Investigación Médica Aplicada FIMA, University of Navarra, Avenida Pio XII s n, 31080 Pamplona, Spain
    Surg Clin North Am 84:673-96. 2004
    ..Combination of biological modifiers, gene therapy, and cell therapy will hopefully provide efficient means to combat inoperable neoplasms in a not-very-distant future...
  56. doi request reprint A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C
    Bruno Sangro
    Liver Unit and HPB Oncology, Clinica Universidad de Navarra, Pamplona, Spain
    J Hepatol 59:81-8. 2013
    ....
  57. ncbi request reprint Gene therapy of cancer based on interleukin 12
    Bruno Sangro
    Liver Unit, Clinica Universitaria de Navarra, and the Division of Hepatology and Gene Therapy, Centro de Investigación Médica Aplicada, Pamplona, Spain
    Curr Gene Ther 5:573-81. 2005
    ..New vectors that might achieve regulated, long-term production of this cytokine might have better results and merit clinical testing...
  58. ncbi request reprint Intratumoural administration of dendritic cells: hostile environment and help by gene therapy
    Eduardo Huarte
    University of Navarra School of Medicine, Gene Therapy Unit, Centro Investigación Médica Aplicada CIMA, Avda Pio XII, 55, 31080 Pamplona, Spain
    Expert Opin Biol Ther 5:7-22. 2005
    ..Several molecular strategies are being devised to interfere with the immunosuppressive actions of these substances and to further enhance the level of anticancer immunity achieved after artificial release of DCs intratumourally...
  59. pmc Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism
    Sara Labiano
    CIMA, Clinica Universidad de Navarra, University of Navarra and IDISNA, Pamplona, Spain
    Oncoimmunology 5:e1062967. 2016
    ..These mechanisms are interpreted as a molecular strategy deployed by tumors to repress lymphocyte co-stimulation via CD137/CD137L...
  60. doi request reprint IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis
    Ivan Martinez-Forero
    Department of Neurology, University of Navarra, Pamplona, Spain
    Eur J Immunol 38:576-86. 2008
    ..Moreover, Stat-3 phosphorylation was lower in controls than in patients after IL-10 stimulation. These results indicate that IL-10 regulatory function is impaired in patients with MS...
  61. pmc Innate functions of immunoglobulin M lessen liver gene transfer with helper-dependent adenovirus
    Carmen Unzu
    Gene Therapy and Hepatology Area, Centre for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain
    PLoS ONE 9:e85432. 2014
    ..In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors. ..
  62. doi request reprint Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes
    Asis Palazon
    CIMA and CUN University of Navarra, Pamplona, Spain
    Cancer Res 71:801-11. 2011
    ..Our findings identify an additional mechanism of action that can explain the immunotherapeutic effects of agonist CD137 antibodies...
  63. pmc Hepatitis C virus structural proteins impair dendritic cell maturation and inhibit in vivo induction of cellular immune responses
    Pablo Sarobe
    Division of Hepatology and Gene Therapy, Fundación para la Investigación Médica Aplicada FIMA, University of Navarra, 31008 Pamplona, Spain
    J Virol 77:10862-71. 2003
    ..These findings are relevant for the design of therapeutic vaccination strategies in HCV-infected patients...
  64. ncbi request reprint Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions
    Pedro Redondo
    Department of Dermatology, University Clinic of Navarra, Pamplona, Navarra, Spain
    J Invest Dermatol 127:1673-80. 2007
    ..These preclinical data and the simplicity of the procedures warrant the design of a pilot clinical trial...
  65. doi request reprint CD137 on inflamed lymphatic endothelial cells enhances CCL21-guided migration of dendritic cells
    Alvaro Teijeira
    Department of Oncology, Centre for Applied MedicalResearch, Clinica Universidad de Navarra, University of Navarra, Pio XII, Pamplona, Spain
    FASEB J 26:3380-92. 2012
    ..Collectively, our results demonstrate that the inflammatory function of lymphatic vessels can be regulated by CD137...
  66. doi request reprint Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)
    Carlos Alfaro
    Division of Gene Therapy and Hepatology, Centre for Applied Medical Research CIMA, Pamplona, Spain Department of Oncology, University Clinic of Navarra, Pamplona, Spain Department of Immunology, University Clinic of Navarra, Pamplona, Spain
    Clin Cancer Res 22:3924-36. 2016
    ..The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes...
  67. pmc Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti-PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells
    Alfonso R Sánchez-Paulete
    Division of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra, and Instituto de Investigación Sanitaria de Navarra IdISNA, Pamplona, Spain
    Cancer Discov 6:71-9. 2016
    ....
  68. doi request reprint Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins
    Miguel F Sanmamed
    Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain Centro de Investigación Médica Aplicada CIMA, Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 20:5697-707. 2014
    ..It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden...
  69. ncbi request reprint Interleukin-15 in gene therapy of cancer
    Maria C Ochoa
    Center for Applied Medical Research, University of Navarra, Avda Pio XII, 55 31008 Pamplona, Spain
    Curr Gene Ther 13:15-30. 2013
    ..Detailed mechanistic knowledge of IL-15 biology is envisaged to make the most of a powerful immunotherapeutic tool ranked as one of the most promising for cancer immunotherapy...
  70. pmc A network analysis of the human T-cell activation gene network identifies JAGGED1 as a therapeutic target for autoimmune diseases
    Ricardo Palacios
    Department of Neurology, Clinica Universitaria de Navarra and Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    PLoS ONE 2:e1222. 2007
    ..This study illustrates how network analysis can predict therapeutic targets for immune intervention and identified the immunomodulatory properties of Jagged1 making it a new therapeutic target for MS and other autoimmune diseases...
  71. doi request reprint Deciphering CD137 (4-1BB) signaling in T-cell costimulation for translation into successful cancer immunotherapy
    Alfonso R Sánchez-Paulete
    Division of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain
    Eur J Immunol 46:513-22. 2016
    ..Ongoing phase II clinical trials with agonist antibodies and the presence of CD137 sequence in these successful chimeric antigen receptors highlight the importance of CD137 in oncoimmunology. ..
  72. ncbi request reprint Gene therapy of cancer with interleukin-12
    Guillermo Mazzolini
    Division of Hepatology and Gene Therapy, Department of Medicine, Centro de Investigación Médica Aplicada FIMA, School of Medicine and Clinica Universitaria, University of Navarra, Pamplona, Spain
    Curr Pharm Des 9:1981-91. 2003
    ....
  73. doi request reprint Direct effects of type I interferons on cells of the immune system
    Sandra Hervas-Stubbs
    Division of Gene Therapy and Hepatology, Centre for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain
    Clin Cancer Res 17:2619-27. 2011
    ..Importantly, IFNs-I also increase antigen presentation of the tumor cells to be recognized by T lymphocytes. These IFN-driven immunostimulatory pathways offer opportunities to devise combinatorial immunotherapy strategies...
  74. doi request reprint Lysine 63 polyubiquitination in immunotherapy and in cancer-promoting inflammation
    Ivan Martinez-Forero
    CIMA and Clinica Universitaria, Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 15:6751-7. 2009
    ..The elements of this new signaling paradigm offer the opportunity for therapeutic exploitation and drug discovery...
  75. pmc Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011
    Ivan Martinez Forero
    Centro de Investigación Médica Aplicada, Universidad de Navarra, Avda Pio XII, 55, 31008 Pamplona, Spain
    J Transl Med 10:108. 2012
    ..The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace...
  76. doi request reprint Porphobilinogen deaminase over-expression in hepatocytes, but not in erythrocytes, prevents accumulation of toxic porphyrin precursors in a mouse model of acute intermittent porphyria
    Carmen Unzu
    Division of Gene Therapy and Hepatology, Center for Applied Medical Research, University of Navarra, Avda Pio XII 55, Pamplona, Spain
    J Hepatol 52:417-24. 2010
    ..Our study aimed to assess the protective effects of bone marrow transplantation or PBGD gene transfer into the liver against phenotypic manifestations of acute porphyria attack induced in an AIP murine model...
  77. doi request reprint Immunotherapy for neurological diseases
    Pablo Villoslada
    Department of Neuroscience, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    Clin Immunol 128:294-305. 2008
    ....
  78. ncbi request reprint Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors
    Bruno Sangro
    Liver Unit, Division of Gene Therapy, Department of Internal Medicine, Clinica Universitaria, University of Navarre, Ap 4209 Pamplona 31080, Spain
    J Clin Oncol 22:1389-97. 2004
    ..To evaluate the feasibility and safety of intratumoral injection of an adenoviral vector encoding human interleukin-12 genes (Ad.IL-12) and secondarily, its biologic effect for the treatment of advanced digestive tumors...
  79. doi request reprint Molecular pathways: hypoxia response in immune cells fighting or promoting cancer
    Asis Palazon
    Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    Clin Cancer Res 18:1207-13. 2012
    ..This review focuses on changes induced by hypoxia in immune cells infiltrating solid malignancies. Such changes may either promote or fight cancer, and thus are important for immunotherapy...
  80. doi request reprint Changing the tumor microenvironment: new strategies for immunotherapy
    Pedro Berraondo
    Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra Clinic, University of Navarra, Pamplona, Navarra, Spain
    Cancer Res 72:5159-64. 2012
    ..Excellent targets for immunotherapeutic intervention were identified, and a number of therapeutic strategies under translation from mouse to human were presented...
  81. ncbi request reprint Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma
    Susana Inoges
    Lab of Immunotherapy, Oncology Division, Center for Applied Medical Research CIMA, Avda Pio XII, 55, 31008 Pamplona Navarra, Spain
    J Natl Cancer Inst 98:1292-301. 2006
    ..Idiotype vaccines can elicit specific immune responses and molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven...
  82. ncbi request reprint Bone-marrow-derived cell differentiation into microglia: a study in a progressive mouse model of Parkinson's disease
    Manuel Rodriguez
    Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain
    Neurobiol Dis 28:316-25. 2007
    ..The precise role of such a cell inflow into the brain requires further study. Nevertheless, this may represent an opportunity to develop neuroprotective therapeutic strategies for PD...
  83. pmc Immunotherapy and immunoescape in colorectal cancer
    Guillermo Mazzolini
    Liver Unit, Facutad de Ciencias Biomédicas, Universidad Austral, Av Presidente Perón 1500, 1635 Derqui Pilar, Buenos Aires, Argentina
    World J Gastroenterol 13:5822-31. 2007
    ....
  84. ncbi request reprint Improving efficacy of interleukin-12-transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens
    Iñigo Tirapu
    Gene Therapy Division, Fundacion para la Investigacion Medica Aplicada, University of Navarre, Irunlarrea s n 31008 Pamplona, Navarre, Spain
    Int J Cancer 110:51-60. 2004
    ..Supplementary Material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html...
  85. ncbi request reprint MAGE antigens: therapeutic targets in hepatocellular carcinoma?
    Pablo Sarobe
    J Hepatol 40:155-8. 2004
  86. ncbi request reprint [Role of interleukin-12 in cancer immunotherapy]
    Guillermo Mazzolini
    Medicina (B Aires) 64:77-8. 2004
  87. ncbi request reprint Immunosuppression routed via the kynurenine pathway: a biochemical and pathophysiologic approach
    Alvaro Gonzalez
    Laboratory of Biochemistry, University Clinic of Navarra, Avda Pio XII 36, Pamplona 31008, Spain
    Adv Clin Chem 45:155-97. 2008
    ..The incorrect activation or blockade suppressive properties of the kynurenine pathway are also implicated in a number of other diseases such as AIDS or autoimmune diseases...