
Immunology, Transplantation and Infectious diseases
Experimental hematology

The main research focus of the lab is the development, preclinical and clinical validation of T-cell based gene therapy approaches to treat cancer. We started the preclinical and clinical use of suicide gene therapy applied to allogeneic stem cell transplantation (allo-HSCT). This approach aims at benefitting from the graftversus-leukemia potential of allogeneic lymphocytes in the context of allo-HSCT, while selectively controlling graft-versus-host disease, their major complication. Pioneered in IRCCS Ospedale San Raffaele in the ‘90s (Bonini et al., Science 1997), optimized and tested in different academic and industry-sponsored clinical trials, the suicide gene therapy approach obtained approval from EMA in 2016, thus representing the first cell based gene therapy product approved for cancer patients in Europe. The many lessons learned with this first project have been more recently exploited in innovative projects designed to redirect T cell specificity against tumor antigens.
Research activity
Recently we developed the TCR gene editing approach (Provasi, Genovese et al., Nat Med 2012; Mastaglio et al., Blood 2017). With this project we completely substitute T cell specificity by editing the genome of T cells with artificial nucleases and viral vectors, thus generating tumor-specific T lymphocytes.
The Immunomonitoring sub-Unit of the lab is dedicated to the identification of immunological correlates with clinical outcome in the context of allo-HSCT, cellular therapy and gene therapy.
Recently, we showed that central memory (TCM) and memory stem T cells (TSCM) are endowed with high expansion and persistence ability, and innovative protocols for their genetic engineering have been developed (reviewed in Gattinoni et al., Nat Med 2017).
The major aim of the lab today, is to actively participate to the exciting transition of cellular therapy from the investigational phase to the phase of real life by developing and validating innovative cellular therapy products.
Petersdorf EW, et.al. Role of HLA-B exon 1 in graft versus-host disease after unrelated haemopoietic cell transplantation: a retrospective cohort study. Lancet Haematol. 2020 Jan;7(1):e50-e60. doi: 10.1016/S2352-3026(19)30208-X. Epub 2019 Oct 25.
Cianciotti B et al. and Bonini C. CD4+ memory stem T cells recognizing citrullinated epitopes are expanded in patients with Rheumatoid Arthritis and sensitive to TNF-α blockade. Arthritis Rheumatol. 2020 Apr;72(4):565-575. doi: 10.1002/art.41157. Epub 2020 Mar 5.
Arcangeli S, Falcone L, Camisa C, De Girardi F, Biondi M, Ciceri C, Bonini C, Bondanza A, Casucci M. Next-generation manufacturing protocols enriching TSCM CAR T cells can overcome disease-specific T cell defects in cancer patients. Front Immunol. 2020 Jun 19;11:1217. doi: 10.3389/fimmu.2020.01217.
Manfredi F, Cianciotti BC, Potenza A, Tassi E, Noviello M, Biondi A, Ciceri F, Bonini C, Ruggiero E, TCR redirected T cells for cancer treatment: Acheivements, hurdles and goals. Front Immunol. 2020 Sep 3; 11: 1689. doi: 10.3389/fimmu.2020.01689. eCollection 2020.PMID: 33013822
Saidu NEB, Bonini C, Dickinson A, Grce M, Inngjerdingen M, Koehl U, Toubert A, Zeiser R, Galimberti S. New approaches for the treatment of chronic graft-versus-host disease (cGvHD): current status and future directions. Front Immunol. 2020 Oct 9; 11: 578314. doi: 10.3389/fimmu.2020.578314. eCollection 2020.
Meric-Bernstam F, Larkin J, Tabernero J, Bonini C. Enhancing Antitumour Efficacy with Immunotherapy Combinations. The Lancet 2021 Mar 13;397(10278):1010-1022. doi: 10.1016/S0140-6736(20)32598-8. Epub 2020 Dec 4.
Manfredi F, Abbati D, Cianciotti BC, Stasi L, Potenza A, Ruggiero E, Magnani Z, Carnevale E, Doglio M, Noviello M, Tassi E, Balestrieri C, Buonanno S, Clemente F, De Lalla C, Protti MP, Mondino A, Casorati G, Dellabona P, Bonini C. Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells. Eur J Immunol. 2021 Jun 3. doi: 10.1002/eji.202049103. Online ahead of print. PMID: 34081326
Greco R, Lorentino F, Albanese S, Lupo Stanghellini MT, Giglio F, Piemontese S, Clerici D, Lazzari L Marcatti M, Mastaglio S, Xue E, Farina F, Pavesi F, Assanelli A, Carrabba M, Marktel S, Vago L, Bonini C, Corti C, Bernardi M, Ciceri F , Peccatori J. Post-Transplant Cyclophosphamide and Sirolimus based Graft-versus-Host-Disease Prophylaxis in Allogeneic Stem Cell Transplant. Transplant Cell Ther. 2021 Jun 1:S2666-6367(21)00942-8. doi: 10.1016/j.jtct.2021.05.023.
Consonni M, Garavaglia C, Grilli A, de Lalla C, Mancino A, Mori L, De Libero G, Montagna D, Lombardo A, Casucci M, Serafini M, Bonini C, Häussinger D, Ciceri F, Bernardi M, Mastaglio S, Bicciato S, Dellabona P, Casorati G. Donor-unrestricted targeting of CD1c-expressing leukemia by human T cells engineered with a lipid-specific TCR. Nat. Comm 2021 Aug 11;12(1):4844. doi: 10.1038/s41467-021-25223-0.
Serpenti F, Lorentino F, Marktel S, Milani R, Messina C, Greco R, Girlanda S, Clerici D, Giglio F, Liberatore C, Farina F, Mastaglio S, Piemontese S, Guggiari E, Lunghi F, Marcatti M, Carrabba M, Bernardi M, Bonini C, Assanelli A, Corti C, Peccatori J, Ciceri F, Lupo-Stanghellini MT. Immune Reconstitution-based score for risk stratification of Chronic Graft-Versus-Host Disease patients. Front Oncol. 2021 Jul 22;11:705568. doi: 10.3389/fonc.2021.705568. eCollection 2021.
Siracusano G, Brombin C, Pastori C, Cugnata F, Noviello M, Tassi E, Princi D, Cantoni D, Malnati M, Maugeri N, Bozzi C, Saretto G, Clementi N, Mancini N, Uberti Foppa C, Temperton NJ, Bonini C, Di Serio C, Lopalco L. Profiling antibody response patterns in COVID-19: spike S1-reactive IgA signature in the evolution of SARS-CoV-2 infection. Front Immunol. 2021 Nov 3;12:772239. doi: 10.3389/fimmu.2021.772239. eCollection 2021.
Greco B, Malacarne V, De Girardi F, Scotti GM, Manfredi F, Angelino E, Sirini C, Camisa B, Falcone L, Moresco MA, Paolella K, Di Bono M, Norata R, Sanvito F, Arcangeli S, Doglioni C, Ciceri F, Bonini C, Graziani A, Bondanza A, Casucci M Disrupting N-glycan expression on tumor cells boosts chimeric antigen receptor T cell efficacy 1 against solid malignancies. Sci Transl Med. 2022 Jan 19;14(628):eabg3072. doi: 10.1126/scitranslmed.abg3072. Epub 2022 Jan 19.
Ruggiero E, Carnevale E, Prodeus A, Magnani ZI, Camisa B, Merelli I, Politano C, Stasi L, Potenza A, Cianciotti BC, Manfredi F, Di Bono M, Vago L, Tassara M, Mastaglio S, Ponzoni M, Sanvito F, Liu D, Balwani I, Galli R, Genua M, Ostuni R, Doglio M, O’Connell D, Dutta I, Yazinski SA, McKee M, Arredouani MS, Schultes B, Ciceri F, Bonini C CRISPR-based gene disruption and integration of high-avidity, WT1-specific T cell receptors improve anti-tumor T cell function. Sci Transl Med. 2022 Feb 9;14(631):eabg8027. doi: 10.1126/scitranslmed.abg8027. Epub 2022 Feb 9
Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, Chabannon C, Ciceri F, Corbacioglu S, Ellard R, Sanchez-Guijo F, Jäger U, Hildebrandt M, Hudecek M, Kersten MJ, Köhl U, Kuball J, Mielke S, Mohty M, Murray J, Nagler A, Rees J, Rioufol C, Saccardi R, Snowden JA, Styczynski J, Subklewe M, Thieblemont C, Topp M, Ispizua ÁU, Chen D, Vrhovac R, Gribben JG, Kröger N, Einsele H, Yakoub-Agha I. Management of Adults and Children receiving CAR T-cell therapy: 2021 Best Practice Recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2021 Dec 16:S0923-7534(21)04876-6. doi: 10.1016/j.annonc.2021.12.003.
Chiara Balestrieri
Bioinformatician
Danilo Abbati
Bioinformatician
Valeria Beretta
Technician
Barbara Camisa
Technician
Neda Mohammadi
Technician
Elena Tiziano
Technician
Matteo Doglio
Postdoc fellow
Zulma Magnani
Technician
Elena Spiga
PhD student
Veronica Valtolina
Technician
Francesco Manfredi
Postdoc fellow
Maddalena Noviello
Research associate
Maria Chiara Maffia
PhD student
Silvia Buonanno
Fellow
Alessia Potenza
Postdoc fellow
Eliana Ruggiero
Project leader
Federica Trippitelli
Fellow
Ivana Centorrino
Fellow
Giulia Di Lullo
Projet Manager
Alessandra Carluccio
Assistant
Marco Lisi
Admistrative staff