Our goal is to gain a deeper understanding of the cellular and molecular mechanisms at the basis of adaptive T cell responses and tumor cell behavior. On one side this unit is dissecting the intracellular events controlling primary T cell activation and differentiation into memory cells, on the other we are tracing their behaviors in vivo in mouse models recapitulating human diseases. To these aims, we have developed tools allowing for the genetic engineering and for the tracing of antigen and tumor-specific T cells in physiological and pathological conditions.
Current efforts are focused on two distinct and yet interconnected lines of research.
The first relates to the characterization of the role of mTOR, STAT3 and Sin3A in primary lymphocyte differentiation and in transformed cell behavior.
The second aims at validating novel adoptive T cell therapies based on the combination of engineered T cells with tumor-stroma targeting strategies, epigenetic drugs or local fractionated radiotherapy for the cure of solid tumors.
Germano G, Lu S, Rospo G, Lamba S, Rousseau B, Fanelli S, Stenech D, Le DT, Hays J, Totaro MG, Amodio V, Chilà R, Mondino A, Diaz LA Jr, Di Nicolantonio F, Bardelli A. CD4 T Cell-Dependent Rejection of Beta-2 Microglobulin Null Mismatch Repair-Deficient Tumors. Cancer Discov. 2021 Jul;11(7):1844-1859.
Corti A, Sacchi A, Gasparri AM, Monieri M, Anderluzzi G, Colombo B, Gori A, Mondino A, Curnis F. Enhancement of doxorubicin anti-cancer activity by vascular targeting using IsoDGR/cytokine-coated nanogold. J Nanobiotechnology. 2021 May 5;19(1):128.
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 Aug;51(8):1992-2005.
Maes K, Mondino A, Lasarte JJ, Agirre X, Vanderkerken K, Prosper F, Breckpot K. Epigenetic Modifiers: Anti-Neoplastic Drugs With Immunomodulating Potential. Front Immunol. 2021 Mar 30;12:652160. doi: 10.3389/fimmu.2021.652160.
Vokali E., S. Yu, S. Hirosue, M. Rincon-Restrepo, F. Duraes, S. Scherer, P. Corthésy-Henrioud, W. Kilarski, A. Mondino, D. Zehn, S. Hugues, and M. Swartz. Lymphatic endothelial cells prime naïve CD8+ T cells into memory cells under steady-state conditions, Nature Communications (2020)11:538
Mondino A., and T. Manzo. To remember or to forget: the role of good and bad memories in adoptive T cell therapy for tumors. Front. Immunol., 27 August 2020.
Gambi G, Di Simone E, Basso V, Ricci L, Wang R, Verma A, Elemento O, Ponzoni M, Inghirami G, Icardi L*, Mondino A*. The transcriptional regulator Sin3A contributes to the oncogenic potential of STAT3. Cancer Res. 2019 Jan 28. pii: canres.0359.2018. *co-last
Terrazzini N, Mantegani P, Kern F, Fortis C, Mondino A*, Caserta S*. Interleukin-7 Unveils Pathogen-Specific T Cells by Enhancing Antigen-Recall Responses. J Infect Dis. 2018 May 25;217(12):1997-2007. *co-last
Elia AR, Grioni M, Basso V, Curnis F, Freschi M, Corti A*, Mondino A*, Bellone M*. Targeting Tumor Vasculature with TNF Leads Effector T Cells to the Tumor and Enhances Therapeutic Efficacy of Immune Checkpoint Blockers in Combination with Adoptive Cell Therapy. Clin Cancer Res. 2018 May 1;24(9):2171-2181 *co-last
Mondino A, Vella G, Icardi L. Targeting the tumor and its associated stroma: one and one can make three in adoptive T cell therapy of solid tumors. Cytokine & Growth Factor Reviews. Cytokine Growth Factor Rev. 2017 Aug;36:57-65.
Manzo T, Sturmheit T, Basso V, Petrozziello E, Hess Michelini R, Riba M, Freschi M, Elia AR, Grioni M, Curnis F, Protti MP, Schumacher TN, Debets R, Swartz MA, Corti A, Bellone M, Mondino A. T cells redirected to a minor histocompatibility antigen instruct intratumoral TNF-α expression and empower adoptive cell therapy for solid tumors. Cancer Res. 2017 Feb 1;77(3):658-671.
Bonini C, Mondino A. Adoptive T-cell therapy for cancer: the era of engineered T cells. European J. Immunol. 2015 Sep;45(9):2457-69.
Petrozziello E, Sturmheit T, Mondino A. Exploiting cytokines in adoptive T cell therapy of cancer. Immunotherapy 2015 Jun;7(5):573-84.
Pilipow K, Basso V, Migone N, Mondino A. Monoallelic germline TSC1 mutations are permissive for T lymphocyte development and homeostasis in Tuberous Sclerosis Complex individuals. PLoS One. 2014 Mar 14;9(3):e91952.
Hess Michelini R, Manzo T, Sturmheit T, Basso V, Rocchi M, Freschi M, Listopad J, Blankenstein T, Bellone M, Mondino A. Vaccine-instructed intratumoral IFN-γ enables regression of autochthonous mouse prostate cancer in allogeneic T cell transplantation. Cancer Res. 2013 Aug 1;73(15):4641-52.
Tomasoni R, Basso V, Pilipow K, Sitia G, Saccani S, Agresti A, Mietton F, Natoli G, Colombetti S*, Mondino A*. Rapamycin-sensitive signals control TCR/CD28-driven Ifng, Il4 and Foxp3 transcription and promoter region methylation. Eur J Immunol. 2011 Jul;41(7):2086-96. (*co-last)