Department of Functional Immuncell-Modulation
Prof. Luca Gattinoni is head of the department for Functional Immune Cell Modulation at the Regensburg Center for Interventional Immunology.
He graduated from the University of Milan School of Medicine with distinction in 1998 and completed his residency in Medical Oncology at the National Cancer Institute (INT) Milan in 2003.
Prof. Gattinoni received postdoctoral training in Cellular Immunotherapy and Tumor Immunology at the Surgery Branch of the U.S. National Cancer Institute (NCI, NIH) from 2003-2008.
He remained at the NCI until 2019 as Staff Scientist (2008-2013) and NIH Stadtman Investigator (2013-2019).
His honors include the 2004 SITC Presidential Award, the 2012 Wilson S. Stone Memorial Award and the 2013 NCI Director’s Intramural Innovation Award.
The Department of Functional Immune Cell Modulation (FICM) is engaged in the development of T cell-based immunotherapies for the treatment of patients with advanced tumors.
The research focuses on T cell fate reprogramming and is organized in three main areas:
The Basic Discovery Program investigates the molecular networks orchestrating T cell differentiation and stemness and develops novel approaches to modulate these pathways in antitumor T cells to enhance their therapeutic efficacy. Strategies encompass the manipulation of transcription factors (Gattinoni et al. Nature Med, 2009; Ji et al., Nature Immunol, 2013; Gautam et al., Nature Immunol, 2019) epigenetic regulators (Ji et al., Nature Commun, 2019), microRNAs (Ji et al. Proc Natl Acad Sci USA, 2015) and metabolic pathways (Sukumar et al., J Clin Invest 2013).
The Preclinical Development Program translates these reprogramming approaches from bench to bedside by implementing them in human T cells and evaluating them in humanized xenograft models (Gattinoni et al., Nature Med 2011).
The Clinical Cell Manufacturing Program is devoted to scaling-up these technologies for direct application in early phase 1/2 clinical trials by developing GMP-grade cell processing protocols and standard operation procedures (Sabatino et al. Blood 2016).
A major area of current investigation at FICM is the development of immunotherapies based on the adoptive transfer of T memory stem (TSCM) cells (Gattinoni et al., Nature Med, 2017). A clinical-grade process for the manufacturing of CAR-modified TSCM has been successfully developed. This innovative platform will serve as a launching pad for the next wave of adoptive TSCM-based immunotherapies.
- Yao C, Sun HW, Lacey NE, Ji Y, Moseman EA, Shih HY, Heuston EF, Kirby M, Anderson S, Cheng J, Khan O, Handon R, Reilley J, Fioravanti J, Hu J, Gossa S, Wherry EJ, Gattinoni L, McGavern DB, O’Shea JJ, Pamela L. Schwartzberg PL, Wu T. Single-Cell RNA-Seq Reveals TOX as a key regulator of CD8+ T cell persistence in chronic Infection. Nature Immunol (2019) 20:890–901
- Ji Y, Fioravanti J, Zhu W, Wang H, Wu T, Hu J, Lacey NE, Gautam S, Le Gall J, Yang X, Hocker JD, Escobar TM, He S, Dell’Orso S, Hawk NV, Kapoor V, Telford WG, Di Croce L, Muljo SA, Zhang Y, Sartorelli V, Gattinoni L. miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of T cell fate. Nat Commun (2019) 10:2157
- Gautam S, Fioravanti J, Zhu W, Le Gall JB, Brohawn P, Lacey NE, Hu J, Hocker JD, Hawk NV, Kapoor V, Telford WG, Gurusamy D, Yu Z, Bhandoola A, Xue HH, Roychoudhuri R, Higgs BW, Restifo NP, Bender TP, Ji Y, Gattinoni L. The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity. Nature Immunol (2019) 20:337–349
- He S, Liu Y, Meng L, Sun H, WangY, Ji Y, Purushe J, Chen P, Li C, Madzo J, Issa JP, Soboloff J, Reshef R, Moore BB, Gattinoni L, Zhang Y. Ezh2 Phosphorylation State Determines its Capacity to Maintain CD8+ T Memory Precursors for Antitumor Immunity. Nature Commun (2017) 8:2125
- Gattinoni L, Speiser DE, Lichterfeld M, Bonini C. T memory stem cells in health and disease. Nature Med (2017) 23:18–27
- WuT, JiY, Moseman EA, Xu HC, ManglaniM, KirbyM, AndersonSM, HandonR, KenyonE, ElkahlounA, Wu W, LangPA, GattinoniL, McGavernDB, SchwartzbergPL. The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Science Immunol (2016) 1: eaai8593
- Sabatino M, Hu J, Sommariva M, Gautam S, Fellowes V, Hocker JD, Dougherty S, Qin H, Klebanoff CA, Fry TJ, Gress RE, Kochenderfer JN, Stroncek DF, Ji Y, Gattinoni L. Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood (2016) 128:519–528
- Roychoudhuri R, Clever D, Li P, Wakabayashi Y, Quinn KM, Klebanoff CA, Ji Y, Sukumar M, Eil RL, Yu Z, Spolski R, Palmer DC, Pan JH, Patel SJ, Macallan DC, Fabozzi G, Shih HY, Kanno Y, Muto A, Zhu J, Gattinoni L, O'Shea JJ, Okkenhaug K, Igarashi K, Leonard WJ, Restifo NP. BACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancers. Nature Immunol (2016) 17:851–860
- Sukumar M, Liu J, Mehta GU, Patel SJ, Roychoudhuri R, Crompton JG, Klebanoff CA, Ji Y, Li P, Yu Z, Whitehill GD, Clever D, Eil RL, Palmer DC, Mitra S, Rao M, Keyvanfar K, Schrump DS, Wang E, Marincola FM, Gattinoni L, Leonard WJ, Muranski P, Finkel T, Restifo NP. Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy. Cell metab (2016) 23:63–76
- Ji Y, Wrzesinski C, Yu Z, Hu J, Gautam S, Hawk NV, Telford WG, Palmer DC, Franco Z, Sukumar M, Clever D, Roychoudhuri R, Klebanoff CA, Surh CD, Waldmann, TA, Restifo, NP, Gattinoni L. miR-155 augments CD8+ T cell anti-tumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines. Proc Natl Acad Sci USA (2015) 112:476–481
- Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, Roychoudhuri R, Palmer DC, Muranski P, Karoly ED, Mohney RP, Klebanoff CA, Lal A, Finkel T, Restifo NP, Gattinoni L. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and anti-tumor function. J Clin Invest (2013) 123:4479–4488
- Dudda JC, Salaun B, Ji Y, Palmer DC, Monnot GC, Merck E, Boudousquie C, Utzschneider DT, Escobar TM, Perret R, Muljo SA, Hebeisen M, Rufer N, Zehn D, Donda A, Restifo NP, Held W, Gattinoni L, Romero P.MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity (2013) 18:742−753
- Gattinoni L, Klebanoff CA, Restifo NP. Paths to stemness: building the ultimate anti-tumour cell. Nature Rev Cancer (2012) 12:671–684
- Ji Y, Pos Z, Rao M, Klebanoff CA, Yu Z, Sukumar M, Reger RN, Palmer DC, Borman ZA, Muranski P, Wang E, Schrump DS, Marincola FM, Restifo NP, Gattinoni L. Repression of the DNA-binding inhibitor Id3 by Blimp1 limits the formation of memory CD8+ T cells. Nature Immunol (2011)12:1230–1237
- Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick, E, Yu Z, Carpenito C, Wang E, Douek DC, Price DA, June CH, Marincola FM, Roederer M, Restifo NP. A human T cell memory subset with stem cell-like properties. Nature Med (2011)17:1290–1297
- Gattinoni L, Klebanoff CA, Restifo NP. Pharmacologic Induction of CD8+ T cell memory: Better Living through chemestry. Science Transl Med (2009)1:ps12
- Gattinoni L, Zhong XS, Palmer DC, Ji Y, Hinrichs CS, Yu Z, Wrzesinski C, Boni A, Cassard L, Church L, Paulos CM, Muranski P, Restifo NP. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nature Med (2009)15:808–813
- Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nature Rev Immunol (2006)6:383–393
- GattinoniL, FinkelsteinSE, Klebanoff CA, AntonyPA, PalmerDC, SpiessPJ, HwangLN, YuZ, WrzesinskiC, Heimann DM, SurhCD, RosenbergSA, Restifo NP. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med (2005)202:907–912
- Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, Finkelstein SE, Theoret MR, Rosenberg SA, Restifo NP. Acquisition of full effector function in vitroparadoxicallyimpairs the in vivoantitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest. (2005)115:1616–1626
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