Eliana Ruggiero RicercatoreMedicina

RESEARCH ACTIVITY

Curriculum Vitae

Publications

RESEARCH ACTIVITY

Genetically modified T cells represent a new class of living drugs endowed with two highly relevant features: the power to persist long-term in the body patrolling for tumor recurrence and the ability to recognize a wide array of target antigens through the T cell receptor (TCR). Technologies based on the transfer of TCRs can effectively redirect some of the most potent player of our immune system against virtually all tumor antigens, including mutated and intracellular proteins. Unfortunately, the paucity of tumor-specific receptors is still impairing the wide range exploitation of TCR-based treatments. Novel strategies aiming at the detection of high-avidity tumor-specific TCRs are strictly required to broaden the applicability of TCR gene therapy as a standard immunotherapeutic approach for cancer.

RESEARCH ACTIVITY

Our laboratory has a great interest toward the implementation of novel approaches for boosting TCR-based immunotherapies. In particular, our research is focused on the study of tumor antigenicity and on the characterization of tumor-specific T cell populations. Our goal is to build and validate in vitro and in vivo a collection of TCR-engineered T cells, specific for different target antigens expressed by hot and cold tumors, able to kill tumor cells and prevent disease relapse.

Curriculum Vitae

Academic Qualifications

2008-2013                       PhD in Biology, University of Heidelberg “Ruprecht-Karls-Universität Heidelberg”, Germany

2005-2007                       M. Sc. in Pharmaceutical Biotechnology, University of Rome “La Sapienza”

Professional Experience

2017-present                    Project Leader of the Research Alliance with Intellia Therapeutics at Ospedale San Raffaele (Milan) in the Experimental Hematology Unit (Prof. Chiara Bonini’s laboratory)

02/2015-2017                  Post-doctoral Fellow at Ospedale San Raffaele (Milan) in the Experimental Hematology Unit (Prof. Chiara Bonini’s laboratory)

03/2013-01/2015             Postdoctoral Fellow at German Cancer Research Center and National Center for Tumor Diseases (Heidelberg, Germany) in the department of Translational Oncology (Prof. Dr. Christof von Kalle’s and Dr. Manfred Schmidt’s laboratory)

09/2008-02/2013             PhD Student at German Cancer Research Center and National Center for Tumor Diseases (Heidelberg, Germany) in the department of Translational Oncology (Prof. Dr. Christof von Kalle’s and Dr. Manfred Schmidt’s laboratory)

07/2007-08/2008             Post-graduate fellow at Istituto Superiore di Sanità (Rome) in the division of Pathogenesis of Retroviruses (Dr. Maurizio Federico’s laboratory)

02/2005-07/2007             Master Student at Istituto Superiore di Sanità (Rome) in the division of Pathogenesis of Retroviruses (Dr. Maurizio Federico’s laboratory)

03/2004-02/2005             Bachelor Student at Istituto Superiore di Sanità (Rome) in the division of Pathogenesis of Retroviruses (Dr. Maurizio Federico’s laboratory)

 

Grants

Finalizzata-GR 2016 (GR-2016-02364847)

H2020 Marie Skłodowska-Curie Individual Fellowships 2016

International Cancer Research Fellowship iCARE 2015

Helmholtz Alliance Immunotherapy of Cancer 2013

Helmholtz Alliance Immunotherapy of Cancer (2010-2012)

Filas fellowship 2008

 

Awards

2020: Excellence in Research Award - American Society for Gene and Cell Therapy (ASGCT)

2020: Travel Grant – American Society for Gene and Cell Therapy (ASGCT)

2019: World Immunotherapy Council (WIC) Young Investigator 2019

2019: Best Springer Poster Award – EBMT 2019

2012: Travel Grant - Deutsche Gesellschaft für Gentherapie (DGGT)

Publications

  1. Russo F., Ruggiero E., et al. "Editing T-cell repertoire by thymic epithelial cell-directed gene transfer abrogates risk of Type 1 Diabetes development.” Mol Ther Methods Clin Dev 2022 May 4;25:508-519.  doi: 10.1016/j.omtm.2022.04.017
  2. Donnadieu E…Ruggiero E., et al. “Time to Evolve: Predicting engineered-T cell-associated toxicity with   next-generation models” J Immunother Cancer 2022 May;10(5):e003486.  doi: 10.1136/jitc-2021-003486
  3. Guedan S. … Ruggiero E., et al. “Time 2EVOLVE – Predicting efficacy of engineered T cells: how far is the bench from the bedside?” J Immunother Cancer 2022 May;10(5):e003487.  doi: 10.1136/jitc-2021-003487
  4. Feola S. Chiaro J., Martins B., Russo S., Fusciello M., Ylosmaki E., Bonini C., Ruggiero E., et al. “A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines”. Elife 2022 Mar 22;11:e71156. doi: 10.7554/eLife.71156
  5. Ruggiero E., et al. “CRISPR-based gene disruption and integration of high-avidity, WT1-specific T cell receptors improve antitumor T cell function”. Sci Transl Med. 2022 Feb 9;14(631):eabg8027. doi: 10.1126/scitranslmed.abg8027
  6. Manfredi F, Abbati D, Cianciotti BC, Stasi L, Potenza A, Ruggiero E, et al. “Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells”. Eur J Immunol. 2021 Aug;51(8):1992-2005. doi: 10.1002/eji.202049103. IF:5,53
  7. Xydia M.*, Rahbari R.*, Ruggiero E.*, et al. “Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients” Nat Commun 12, 1119 (2021). doi:10.1038/s41467-021-21297-y
  8. Manfredi F, …, Bonini C*, Ruggiero E*. “TCR redirected T cells for cancer treatment: achievements, hurdles and goals” Fron Immunol. 2020 Sep 3,11:1689. doi: 10.3389/fimmu.2020.01689
  9. Cianciotti BC, Ruggiero E, et al. “CD4+ Memory Stem T Cells Recognizing Citrullinated Epitopes Are Expanded in Patients With Rheumatoid Arthritis and Sensitive to Tumor Necrosis Factor Blockade” Arthritis Rheumatol. 2020 Apr;72(4):565-575. doi: 10.1002/art.41157
  10. Noviello M*, Manfredi F*, Ruggiero E, et al. “Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT.” Nat Commun. 2019 Mar 25;10(1):1065. https://doi.org/1038/s41467-019-08871-1
  11. Falkenburg F, Ruggiero E, et al. “Prevention and treatment of relapse after stem cell transplantation by cellular therapies.” Bone Marrow Transplant. 2019 Jan;54(1):26-34. doi: 10.1038/s41409-018-0227-0
  12. Della-Torre E, Bozzalla-Cassione E, Ruggiero E, et al. “A CD8α- subset of CD4+SLAMF7+ cytotoxic T cells is expanded in patients with IgG4-Related Disease and selectively decreases following glucocorticoid treatment” Arthritis Rheumatol. 2018 Mar 2. doi: 10.1002/art.40469
  13. Mathew NR, …Ruggiero E et al. “Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD mutant leukemia cells” Nat Med. 2018 Apr 10;24(4):526. doi: 10.1038/nm.4484
  14. Prestipino A, … Ruggiero E, et al.  “Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms” Sci Transl Med. 2018 Feb 21;10(429). doi: 10.1126/scitranslmed.aam7729
  15. Mastaglio S, Genovese P, Magnani Z, Ruggiero E, et al. “ NY-ESO-1 TCR single edited stem and central memory T cells to treat multiple myeloma without graft-versus-host disease." Blood. 2017 Aug 3;130(5):606-618. doi: 10.1182/blood-2016-08-732636.
  16. Oliveira G, Ruggiero E, et al. "Tracking genetically engineered lymphocytes long-term reveals the dynamic of T-cell immunological memory" Sci Transl Med. 2015 Dec 9;7(317):317ra198. doi: 10.1126/scitranslmed.aac8265.
  17. Ruggiero E*, Nicolay JP*, et al. “High-Resolution Analysis of the Human T Cell Receptor Repertoire” Nat Commun. 2015 Sep 1;6:8081. doi: 10.1038/ncomms9081.
  18. Richards DM, Ruggiero E, et al. "The contained self-reactive peripheral T cell repertoire: size, diversity and cellular composition” J Immunol. 2015 Sep 1;195(5):2067-79. doi: 10.4049/jimmunol.1500880
  19. Sundarasetty BS, … Ruggiero E, et al. “Generation of lentivirus-induced dendritic cells under GMP-compliant conditions for Adaptive immune reconstitution against cytomegalovirus after stem cell transplantation” J Transl Med. 2015 Jul 22;13:240. doi: 10.1186/s12967-015-0599-5
  20. Sundarasetty BS, … Ruggiero E, et al. "Lentivirus-induced "Smart" dendritic cells: Pharmacodynamics and GMP-compliant production for immunotherapy against TRP2 positive melanoma" Gene Ther. 2015 May 28. doi: 10.1038/gt.2015.43
  21. Bergot AS, Chaara W, Ruggiero E, et al. "TCR sequences and tissue distribution discriminate the subsets of naïve and activated/memory Treg cells in mice" Eur J Immunol. 2015 May;45(5):1524-34. doi: 10.1002/eji.201445269
  22. Gardyan A, … Ruggiero E, et al. "Identification of NY-BR-1-specific CD4(+) T cell epitopes using HLA-transgenic mice" Int J Cancer. 2015 Jun 1;136(11):2588-97. doi: 10.1002/ijc.29322
  23. Daenthanasanmak A, …Ruggiero E, et al. “Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV” Molecular Therapy - Methods & Clinical Development  1, Article number: 14060 (2015). doi: 10.1038/mtm.2014.60
  24. Martins VC, Ruggiero E, et al. “Thymus-autonomous T cell development in the absence of progenitor import.” J Exp Med. 2012 Jul 30;209(8):1409-17. doi: 10.1084/jem.20120846
  25. Pincha M, … Ruggiero E, et al. “Identity, potency, in vivo viability, and scaling up production of lentiviral vector-induced dendritic cells for melanoma immunotherapy.” Hum Gene Ther Methods. 2012 Feb;23(1):38-55. doi: 10.1089/hgtb.2011.170
  26. Ruggiero E, Toschi E, Federico M. “The Activity of Matrix Metalloproteinase-9 is Part of the Mechanism of Cell-to-Cell HIV-1 Endocytosis in Dendritic Cells.” Curr Drug Discov Technol. 2011 Jun;8(2):112-8. doi: 10.2174/157016311795563893
  27. Muratori C, Ruggiero E, et al. “Human immunodeficiency virus type 1 (HIV-1) protease inhibitors block cell-to-cell HIV-1 endocytosis in dendritic cells.“ J Gen Virol. 2009 Nov;90(Pt 11):2777-87. doi: 10.1099/vir.0.012609-0
  28. Muratori C, Bona R, Ruggiero E, et al. “DC contact with HIV-1-infected cells leads to high levels of Env-mediated virion endocytosis coupled with enhanced HIV-1 Ag presentation.“ Eur J Immunol. 2009 Feb;39(2):404-16. doi: 10.1002/eji.200838751
  29. Ruggiero E, et al. “Virological consequences of early events following the cell-cell contact between HIV-1 infected and uninfected CD4+ cells.” J Virol. 2008 Aug;82(16):7773-89. doi: 10.1128/JVI.00695-08
  30. Muratori C, Sistigu A, Ruggiero E, et al. “Macrophages transmit Human Immunodeficiency Virus Type 1 products to CD4-negative cells: involvement of matrix metalloproteinase 9.” J Virol. 2007 Sep;81(17):9078-87. doi: 10.1128/JVI.00675-07

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