Zell- und Gentherapie
AG Caruana
Unsere Gruppe strebt insbesondere Folgendes an:
- Identifizierung neuer Tumorantigene, welche sich als Zielstruktur für immuntherapeutische Behandlungen eignen
- Entwicklung von immuntherapeutischen Ansätzen basierend auf genmodifizierten Immunzellen, die einen chimären Antigenrezeptor oder T-Zell-Rezeptor tragen, und onkolytischen Viren, wobei auch kombinierte Therapieansätze denkbar sind
- Identifizierung und Evaluierung verschiedener Effektorzelltypen für immuntherapeutische Therapieansätze
- Generierung einer ready-to-use Zellbank zur Bereitstellung einer Überbrückungsstrategie vor weiteren zellbasierten Therapien oder zur Prävention eines Rezidivs
- Entwicklung von Kombinationsstrategien zur Steigerung der Persistenz, Aktivität und Wirksamkeit adoptiv übertragener Immunzellen, um eine langfristige Tumorkontrolle zu erreichen
- Evaluierung der Antitumorwirkung der neu entwickelten Therapieansätze in humanisierten Xenotransplantmodellen und die nachfolgende Translation dieser Therapieansätze in die klinische Anwendung unter Verwendung GMP-gerechter Protokolle und Ausgangsmaterialien
Team der Forschungsgruppe
Leitung
Dr. Ignazio Caruana, PhD
Arbeitsgruppenleiter
Telefon: +49 931-201-27660
Fax: +49 931-201-627660
E-Mail: caruana_i@ukw.de
Ksenia Melzer
Assistenz des Arbeitsgruppenleiters
Telefon: +49 931-201-27214
Fax: +49 931-201-627989
E-Mail: melzer_k@ukw.de
Wissenschaftliche Mitarbeiterinnen und Mitarbeiter
Dr. Stefan Ebert
Postdoc
Telefon: +49 931-201-27734
Fax: +49 931-201-627734
E-Mail: ebert_s2@ukw.de
Mac Dang Giang
Medizinisch-technischer Assistent
Telefon: +49 931-201-27734
E-Mail: mac_d@ukw.de
Dorothee Haas M.Sc.
Naturwissenschaftliche Doktorandin
Telefon: +49 931-201-27925
E-Mail: haas_d3@ukw.de
Lokossou William Sanvi
Naturwissenschaftlicher Doktorand
Telefon: +49 931-201-27925
E-Mail: sanvi_l@ukw.de
Simone Vespa M.Sc.
Naturwissenschaftlicher Doktorand
Exchange PhD Program University of Chieti-Pescara, Italy)
Telefon: +49 931-201-27925
E-Mail: simone.vespa@unich.it
Offene Stellen
Die AG Caruana bietet die Möglichkeit, sich für Stellen zur Durchführung von Doktorarbeiten, Masterarbeiten und verschiedenen Praktika zu bewerben. Grundanforderungen hierfür sind großes Interesse am Forschungsthema und ein hohes Maß an Motivation. Voraussetzungen für eine erfolgreiche Bewerbung sind zudem gute Kommunikationsfähigkeiten in englischer Sprache und die Bereitschaft, in einem dynamischen Umfeld zu arbeiten. Während der Projektarbeit wird die Möglichkeit geboten, an einem innovativen und translationalen Forschungsprojekt mitzuwirken.
Bewerbungen mit Lebenslauf und Motivationsschreiben sollten in englischer Sprache per E-Mail an Dr. Caruana gerichtet werden.
E-Mail: Caruana_I@ukw.de
Publikationen
Publikationen der AG Caruana
Original Studies
C. Giordano, S. Carlomagno, M. Falco, C. Cantoni, M. Vitale, I. Caruana, J. Dirks, A. Serio, L. Muccio, G. Bartalucci, A. Bo, F. Locatelli, C. Bottino, S. Sivori, M. Della Chiesa.
CD94-driven in vitro expansion of highly functional adaptive NKG2C + NKG2A -CD57
+ NK cells from CMV + healthy donors.
Frontiers in Immunology, 2025; in press.
I. Pallavicini, T.M. Frasconi, C. Catozzi, E. Ceccaci, S. Tiberti, D. Haas, J. Samson, C. Heuser-Loy, C.B. Nava Lauson, M. Mangione, E. Preto, A. Bigogno, E. Sala, M. Iannacone, C. Mercurio, L. Gattinoni, I. Caruana, M. Kuka, L. Nezi, S. Minucci, T. Manzo.
Dr. Ignazio Caruana
Curriculum Vitae
University Hospital of Würzburg
8
LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell
responsiveness.
Nature Communication, 2024; 15(1): 7366.
J. Dirks, J. Fischer, J. Klaussner, C. Hofmann, A. Holl-Wieden, V. Buck, C. Klemann, H. Girschick, I. Caruana, F. Erhard and H. Morbach.
Identification of disease-specific TCRs maintaining pathogenic T helper cell responses in postinfectious Lyme Arthritis.
Journal of Clinical Investigation, 2024; e179391.
S. Di Matteo, M.T. Bilotta, A. Pelosi, D. Haas, T. Theinert, G. Weber, P.G. Schlegel, M. Berg, L. Moretta, E. Maggi, B. Azzarone, P. Vacca, N. Tumino, I. Caruana.
Transition to a mesenchymal state in neuroblastoma may be characterized by a high expression of GD2 and by the acquisition of immune escape mechanisms from NK cells.
Frontiers in Immunology, 2024; 15:1382931.
S. Di Matteo, E. Munari, P.F. Fiore, S. Santopolo, C. Sampaoli, A. Pelosi, S. Chouaib, N. Tumino, P. Vacca, F. Mariotti, S. Ebert, M. Machwirth, D. Haas, M. Pezzullo, G. Pietra, M. Grottoli, S. Buart, E. Mortier, E. Maggi, L. Moretta, I. Caruana* and B. Azzarone*.
Role of different forms of IL-15 in human melanoma progression.
Frontiers in Immunology, 2023; 14:1183668.
M. Ruopp, S. Reilander, D. Haas, I. Caruana, D. Kronenberg, W. Schmehl, R. Stange, L. Meinel.
Transdermal carbon monoxide delivery.
Journal of Controlled Released, 2023; 357: 299-308.
C.B. Nava Lauson, S. Tiberti, P. Corsetto, F. Conte, T. Punit, M. Machwirth, S. Ebert, A. Loffreda, L. Scheller, D. Sheta, T. Peters, A.T. Raman, F. Greco, A. Rizzo, A. Beilhack, G. Signori, N. Tumino, P. Vacca, L. McDonnell, A. Raimondi, P.D. Greenberg, J.B. Huppa, S. Cardaci, I. Caruana, S. Rodighiero, L. Nezi, T. Manzo.
Linoleic acid potentiates CD8+ T cell metabolic fitness and anti-tumor immunity.
Cell Metabolism, 2023; 35(4): 633-650.e9.
F. Del Bufalo, B. De Angelis, I. Caruana, G. Del Baldo, M.A. De Ioris, A. Serra, A. Mastronuzzi, M.G. Cefalo, D. Pagliara, M. Amicucci, G. Li Pira, G. Leone, V. Bertaina, M. Sinibaldi, S. Di Cecca, G. Marica, A. Zeinab, L. Iaffaldano, M. Gunetti, S. Iacovelli, R. Bugianesi, S. Macchia, M. Algeri, P. Merli, F. Galaverna, R. Abbas, M.C. Garganese, M.F. Villani, G.S. Colafati, F. Bonetti, M. Rabusin, K. Perruccio, V. Folsi, C. Quintarelli, F. Locatelli.
Third generation GD2-CART01 for relapsed/refractory high-risk neuroblastoma.
New England Journal of Medicine, 2023; 388(14): 1284-1295.
E. de Billy, M. Pellegrino, D. Orlando, G. Pericoli, R. Ferretti, P. Businaro, M.A. Ajmone-Cat, S. Rossi, L.L. Petrilli, N. Maestro, F. Diomedi-Camassei, M. Pezzullo, C. De Stefanis, P. Bencivenga, A. Palma, R. Rota, F. Del Bufalo, L. Massimi, G. Weber, C. Jones, A. Carai, B. De Angelis, I. Caruana, C. Quintarelli, A. Mastronuzzi, F. Locatelli, M. Vinci.
Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent antitumor
activity in diffuse midline glioma H3K27M-mutant.
Neuro-Oncology, 2022; 24(7): 1150-1163.
Dr. Ignazio Caruana
Curriculum Vitae
University Hospital of Würzburg
9
N. Tumino, G. Weber, F. Besi, F. Del Bufalo, V. Bertaina, P. Paci, L. Quatrini, L. Antonucci, M. Sinibaldi, C. Quintarelli, E. Maggi, B. De Angelis, F. Locatelli, L. Moretta, P. Vacca*, I. Caruana*.
Polymorphonuclear myeloid-derived suppressor cells impair the anti-tumor efficacy of
GD2.CAR T-cells in patients with neuroblastoma.
Journal of Hematology & Oncology, 2021; 14(1):191.
F. Nazio, A. Po, L. Abballe, C. Ballabio, F. Diomedi Camassei, M. Bordi, A. Camera, S. Caruso, I. Caruana, M. Pezzullo, C. Ferraina, G. Milletti, M. Gianesello, S. Reddel, C.D. De Luca, D. Ceglie, S. Merinelli, S. Campello, E. Papaleo, E. Miele, A. Cacchione, A. Carai, M. Vinci, E. Velardi, B. De Angelis, L. Tiberi, C. Quintarelli, A. Mastronuzzi, E. Ferretti, F. Locatelli, F. Cecconi.
Targeting cancer stem cells in medulloblastoma by inhibiting AMBRA1 dual function in
autophagy and STAT3 signalling.
Acta Neuropathologica, 2021; 142(3):537-564.
S. Schwinn, Z. Mokhtari, S. Thusek, T. Schneider, A.L. Siren, N. Tiemeyer, I.Caruana, E. Miele, P.G. Schlegel, A. Beilhack, M. Wolfl.
Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for cmyc
amplified medulloblastoma.
Scientific Report, 2021; 11(1):14062.
C.M. Arnone, V.A. Polito, A. Mastronuzzi, A. Carai, F. Diomedi Camassei, L. Antonucci, L.L. Petrilli, M. Vinci, F. Ferrari, E. Salviato, G. Weber, M. Scarsella, C. De Stefanis, C. Quintarelli, M.K. Brenner, S. Gottschalk, V. Hoyos, F. Locatelli, I. Caruana*, F. del Bufalo*.
Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric
high-grade gliomas.
Journal for Immunotherapy of Cancer, 2021; 9(5):e001930.
M. Carinci, B. Testa, M. Bordi, G. Milletti, M. Bonora, L. Antonucci, C. Ferraina, M. Carro, M. Kumar, D. Ceglie, F. Eck, R. Nardacci, F. le Guerroue, S. Petrini, M.E. Soriano, I. Caruana, V. Doria, M. Manifava, C. Peron, M. Lambrughi, V. Tiranti1, C. Beherends, E. Papaleo, P. Pinton, C. Giorgi, N.T. Ktistakis, F. Locatelli, F. Nazio, F. Cecconi.
TFG (TRK-fused gene) regulates ULK1 to promote autophagosome formation through
LC3C binding.
The EMBO journal, 2021; 40(10):e103563.
M. Caforio, C. Sorino, I. Caruana, G. Weber, A. Camera, L. Cifaldi, B. De Angelis, A. Vitale, B.M. Goffredo, R. De Vito, D. Fruci, C. Quintarelli, M. Fanciulli, F. Locatelli, V. Folgiero.
GD2 redirected CAR T and activated NK-cell-mediated secretion of IFNγ overcomes MYCN-dependent IDO1 inhibition, contributing to Neuroblastoma cell immune escape.
Journal for Immunotherapy of Cancer, 2021; 9(3):e001502.
P.F. Fiore, P. Vacca, N. Tumino, F. Besi, A. Pelosi, E. Munari, M. Marconi, I.Caruana, V. Pistoia, L. Moretta, B. Azzarone.
Wilms' Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages.
Cancers (Basel), 2021; 13(2):224.
C. Canzonetta, A. Pelosi, S. Di Matteo, I. Veneziani, N. Tumino, P. Vacca, E. Munari, M. Pezzullo, C. Theuer, R. De Vito, V. Pistoia, L. Tomao, F. Locatelli, L. Moretta, I. Caruana* and B. Azzarone*.
Dr. Ignazio Caruana
Curriculum Vitae
University Hospital of Würzburg
10
Identification of neuroblastoma cell lines with uncommon TAZ+/Mesenchymal Stromal Cell phenotype with strong suppressive activity on Natural Killer cells.
Journal for Immunotherapy of Cancer, 2021; e001313.
S. Pomella, P. Sreenivas, Berkley E. Gryder, L. Wang, D. Milewski, M. Cassandri, K. Baxi, N.R. Hensch, E. Carcarino, Y. Song, H.C. Chen, M.E. Yohe, B.Z. Stanton, B. Amadio, I. Caruana, C. De Stefanis, R. De Vito, F. Locatelli, Y. Chen, E.Y. Chen, P. Houghton, J. Khan, R. Rota, and M.S. Ignatius.
Liaison between SNAI2 and MYOD enhances oncogenesis and suppresses differentiation in Fusion-Negative Rhabdomyosarcoma.
Nature Communication, 2021; 12(1):192.
G. Weber, L. Strocchio, F. Del Bufalo, M. Algeri, D. Pagliara, C.M. Arnone, B. De Angelis, C. Quintarelli, F. Locatelli, P. Merli, I. Caruana.
Identification of new soluble factors correlated with the development of graft failure after haploidentical haematopoietic stem cell transplantation.
Frontiers in Immunology, 2021; 11:613644.
M. Guercio, D. Orlando, S. Di Cecca, M. Sinibaldi, I. Boffa, S. Caruso, Z. Abbaszadeh, A. Camera, B. Cembrola, K. Bovetti, S. Manni, I. Caruana, R. Ciccone, F. Del Bufalo, P. Merli, L. Vinti, K. Girardi, A. Ruggeri, C. De Stefanis, M. Pezzullo, E. Giorda, M. Scarsella, R. De Vito, S. Barresi, A. Ciolfi, M. Tartaglia, L. Moretta, F. Locatelli, C. Quintarelli, and B. De Angelis.
CD28.OX40 co-stimulatory combination is associated with long in vivo persistence and high activity of CAR.CD30 T-cells.
Haematologica, 2021; 106(4):987-999.
L. Simula, M. Corrado, B. Accordi, A. Di Rita, F. Nazio, Y. Antonucci, A. Di Daniele, M. Pigazzi, F. Caicci, M.E. Soriano, I. Caruana, F. Locatelli, F. Cecconi and S. Campello.
JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.
Cell Death & Differentiation, 2020; 27(10):2749-2767.
V.A. Polito, R. Cristantielli, G. Weber, F. Del Bufalo, T. Belardinilli, C.M. Arnone, A. Petretto, L. Antonucci, E. Giorda, N. Tumino, A. Pitisci, B. De Angelis, C. Quintarelli, F. Locatelli and I. Caruana.
Universal ready-to-use immunotherapeutic approach for the treatment of cancer: expanded and activated polyclonal γδ memory T cells.
Frontiers in Immunology, 2019; 10, 2717.
P. D’Acunzo, F. Strappazzon, I. Caruana, G. Meneghetti, L. Simula, G. Weber, F. Del Bufalo, L. Dalla Valle, S. Campello, F. Locatelli and F. Cecconi.
Reversible induction 1 of mitophagy by an optogenetic bimodular system.
Nature Communication, 2019; 10(1):1533.
P. Merli, I. Caruana, R. De Vito, L. Strocchio, G. Weber, F. Del Bufalo, V. Buatois, P. Montanari, M.G. Cefalo, A. Pitisci, M. Algeri, F. Galaverna, C. Quintarelli, V. Cirillo, D. Pagliara, W. Ferlin, M. Ballabio, C. De Min and F. Locatelli.
Role of IFNγ in immune-mediated graft failure occurring after allogeneic hematopoietic stem cell transplantation.
Haematologica, 2019; 104(11):2314-2323.
J. Becher, L. Simula, E. Volpe, C. Procaccini, C. La Rocca, P. D'Acunzo, V. Cianfanelli, F. Strappazzon, I. Caruana, F. Nazio, G. Weber, V. Gigantino, G. Botti, F. Ciccosanti,
Dr. Ignazio Caruana
Curriculum Vitae
University Hospital of Würzburg
11
G. Borsellino, S. Campello, G. Mandolesi, M. De Bardi, G.M. Fimia, M. D'Amelio, F.
Ruffini, R. Furlan, D. Centonze, G. Martino, P. Braghetta, M. Chrisam, P. Bonaldo, G.
Matarese, F. Locatelli, L. Battistini and F. Cecconi.
AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the
FOXO3-FOXP3 Axis.
Developmental Cell, 2018;47(5):592-607.
D. Orlando, E. Miele, B. De Angelis, M. Guercio, I. Boffa, M. Sinibaldi, A. Po, I. Caruana, L. Abbale, A. Carai, S. Caruso, A. Camera, A. Moseley, R.S. Hagedoorn, M.H.M. Heemskerk, F. Giangaspero, A. Mastronuzzi, E. Ferretti, F. Locatelli, C. Quintarelli.
Adoptive immunotherapy in medulloblastoma with T cells redirected toward tumor cells through PRAME-specific αβ TCR gene modification.
Cancer Research, 2018; 78(12): 3337-3349.
C. Quintarelli, D. Orlando, I. Boffa, M. Guercio, V.A. Polito, A. Petretto, C. Lavarello, M. Sinibaldi, G. Weber, F. Del Bufalo, E. Giorda, M. Scarsella, S. Petrini, D. Pagliara, F. Locatelli, B. De Angelis, I. Caruana.
Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma.
Oncoimmunology, 2018; 7(6): e1433518.
P. Bocca, E. Di Carlo, I. Caruana, L. Emionite, M. Cilli, B. De Angelis, C. Quintarelli, A. Pezzolo, L. Raffaghello, F. Morandi, F. Locatelli, V. Pistoa, I. Prigione.
Bevacizumab-mediated tumor vasculature remodelling improves tumor infiltration and antitumor efficacy of GD2-CAR T cells in a human neuroblastoma preclinical model.
OncoImmunology, 2017; 7(1):e1378843.
G. Li Pira, S. Di Cecca, S. Biagini, E. Girolami, E. Cicchetti, V. Bertaina, C. Quintarelli, I. Caruana, B. Lucarelli, P. Merli, D. Pagliara, L.P. Brescia, A. Bertaina, M. Montanari, F. Locatelli. Preservation of Antigen-Specific Functions of αβ T Cells and B Cells
Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy.
Frontier in Immunology, 2017; 8:332.
F. Del Bufalo, T. Manzo, V. Hoyos, Y. Shigeki, I. Caruana, J. Jacot, O. Benavides, D. Rosen, M. K. Brenner.
3D modelling of human cancer: a hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus.
Biomaterials, 2016; 84:76-85.
I. Caruana, B. Savoldo, V. Hoyos, G. Weber, H. Liu, ES Kim, MM Ittmann, D. Marchetti and G. Dotti.
Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes.
Nature Medicine, 2015; 21(5):524-9.
I. Caruana, G. Weber, BC Ballard, MS Wood, B. Savoldo and G. Dotti.
K562-derived whole-cell vaccine enhances antitumor responses of CAR-redirected virus-specific cytotoxic T lymphocytes in vivo.
Clinical Cancer Research, 2015; 21(13):2952-62.
N. Nishio, I. Diaconu, H. Liu, V. Cerullo, I. Caruana, V. Hoyos, L. Bouchier-Haves, B. Savoldo and G. Dotti.
Dr. Ignazio Caruana
Curriculum Vitae
University Hospital of Würzburg
12
Armed oncolytic virus enhances immune functions of chimeric antigen receptor modified T cells in solid tumors.
Cancer Research, 2014; 74(18):5195-205.
C. Geldres, B. Savoldo, V. Hoyos, I. Caruana, M. Zhang, E. Yvon, M. Del Vecchio, C. Creighton, M. Ittmann, S. Ferrone and G. Dotti.
T lymphocytes redirected against the chondritin sulfate proteoglycan-4 control the growth of multiple solid tumors in vitro and in vivo.
Clinical Cancer Research, 2014. 20(4):962-71.
G. Weber, I. Caruana, R.H. Rouce, A.J. Barrett, A.M. Leen, K.R. Rabin, C.M. Bollard.
Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia - implications for immunotherapy.
Clinical Cancer Research, 2013;19(18):5079-91.
G. Weber, U. Gerdemann, I. Caruana, B. Savoldo, N.F. Hensel, K.R. Rabin, E.J. Shpall, J.J. Melenhorst, A.M. Leen, A.J. Barrett and C.M. Bollard.
Generation of multi-leukemia antigen-specific T cells to enhance the graft-versusleukemia effect after allogeneic stem cell transplant.
Leukemia, 2013; 27(7):1538-47.
Reviews
M. Giansanti, T. Theinert, S.K. Boeing, D. Haas, P.G. Schlegel, P. Vacca, F. Nazio* and I. Caruana*.
Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies.
Molecular Cancer, 2023; 22(1):201.
S. Pagotto, P. Simeone, D. Brocco, G. Catitti, D. De Bellis, S. Vespa, N. Di Pietro, L. Marinelli, A. Di Stefano, S. Veschi, L. De Lellis, F. Verginelli, F. Kaitsas, M. Iezzi, A. Pandolfi, R. Visone, N. Tinari, I. Caruana, M. Di Ianni, A. Cama, P. Lanuti, R. Florio.
CAR-T Derived Extracellular Aesicles: a Promising Development of CAR-T Anti-Tumor Therapy.
Cancers, 2023; 15(4):1052.
J. Buechner, I. Caruana, A. Kunkele, S. Rives, K. Vettenranta, P. Bader, C. Peters, A. Baruchel, F. Calkoen.
Chimeric Antigen Receptor T-Cell Therapy in Paediatric B-Cell Precursor Acute Lymphoblastic Leukaemia: Curative Treatment Option or Bridge to Transplant?
Frontiers in Pediatrics, 2022; 9:784024.
A. Pelosi, P.F. Fiore, S. Di Matteo, I. Veneziani, I. Caruana, S. Ebert, E. Munari, L. Moretta, E. Maggi, B.G. Azzarone.
Pediatric tumors-mediated inhibitory effect on NK cells: the case of Neuroblastoma and Wilms’ tumors.
Cancers, 2021; 13(10): 2374.
M. Pellegrino, F. Del Bufalo, B. De Angelis, C. Quintarelli, I. Caruana*, E. de Billy*.
Manipulating the Metabolism to Improve the Efficacy of CAR T-Cell Immunotherapy.
Cells, 2020; 10(1):14.
I. Caruana, L. Simula, F. Locatelli and S. Campello.
T lymphocytes against solid malignancies: winning ways to defeat tumours.
Dr. Ignazio Caruana
Curriculum Vitae
University Hospital of Würzburg
13
Cell Stress, 2018; 2(8):200-12.
I. Caruana, I. Diaconu ans G. Dotti.
From monoclonal antibody to chimeric antigen receptor for the treatment of human malignancies.
Seminars in Oncology, 2014; 41(5):661-6.
Editorial / Commentary
V. Marabitti, I. Caruana*, F. Nazio*.
Should I stay or should I go? Spatio-temporal control of cellular anchorage by hematopoietic factors orchestrates tumor metastatic cascade.
Molecular Cancer, 2023; 22(1):149. (Commentary)
C. Quintarelli, F. Locatelli, I. Caruana, B. De Angelis.
Current challenges in CAR T-cell product cGMP release.
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