Cell and Gene Therapy
AG Caruana
In particular, our group is aiming to:
- identify novel molecules expressed by tumor cells and use them to better and more specifically redirect our new immunotherapeutic approaches,
- improve the efficacy, functionality and safety of immunotherapeutic approaches based on:
- chimeric antigen receptor gene-modified immune cells
- T-cell receptor gene-modified T-lymphocytes
- oncolytic viruses
- combined therapeutic approaches
- generate ready-to-use cellular and gene-modified products as a bridge therapy or to avoid relapse,
- develop combination strategies to increase the persistence, fitness and efficacy of adoptively transferred immune cells to guarantee a stable and durable treatment response,
- and last but not least, translate these approaches from bench to bedside by first evaluating the efficacy of the proposed approaches in preclinical models and subsequently in human clinical trials.
Team
Leader
Dr. Ignazio Caruana, PhD
Principal Investigator / Group Leader
Telefon: +49 931-201-27660
Fax: +49 931-201-627660
E-Mail: caruana_i@ukw.de
Ksenia Melzer
Office administrative AG Caruana
Phone: +49 931 201-27214
E-Mail: melzer_k@ukw.de
Scientific assistants
Dr. Stefan Ebert
Postdoc
Telefon: +49 931-201-27734
Fax: +49 931-201-627734
E-Mail: ebert_s2@ukw.de
Mac Dang Giang
Medical-technical assistant
Telefon: +49 931-201-27734
E-Mail: mac_d@ukw.de
Dorothee Haas M.Sc.
PhD student
Telefon: +49 931-201-27925
E-Mail: haas_d3@ukw.de
Lokossou William Sanvi
PhD student
Telefon: +49 931-201-27925
E-Mail: sanvi_l@ukw.de
Simone Vespa M.Sc.
PhD student
Exchange PhD Program University of Chieti-Pescara, Italy
Telefon: +49 931-201-27925
E-Mail: simone.vespa@unich.it
Career
The Caruana research group offers the possibility to apply for a position to carry out MD or PhD theses, master theses and various internships. Prerequisites are interest and high motivation. A successful applicant should have good communication skills in English and the willingness to work in a dynamic environment. Candidates will be given the opportunity to participate in an innovative translational research project.
Applications including CV and letter of motivation should be addressed in English to Dr. Caruana by email.
E-Mail: caruana_i@ukw.de
Publications
Publications
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.
Partners and Funding
Kontakt, Öffnungszeiten, Sprechzeiten
Address
Kinderklinik und Poliklinik des Universitätsklinikums und der Bayerischen Julius-Maximilians-Universität | Josef-Schneider-Straße 2 | Haus D31 | 97080 Würzburg | Deutschland