Home | Research | Research Divisions | Functional Immune Cell Modulation Functional Immune Cell Modulation Research The Functional Immune Cell Modulation Division is engaged in the development of T cell-based immunotherapies for the treatment of patients with advanced tumors. Our multifaceted approach is organized into three distinct but interconnected programs, each contributing to the overarching goal of enhancing the therapeutic efficacy of T cells against cancer. 01 | Basic Discovery Program In the Basic Discovery Program, we delve deep into the molecular mechanisms that govern T-cell differentiation and stemness. Our mission is to uncover the molecular networks orchestrating these vital processes and develop innovative strategies for modulating them within antitumor T cells. This includes manipulation at various levels, from transcription factors (Gattinoni L. et al, Nature Med, 2009; Ji Y. et al, Nature Immunol, 2013; Gautam S. et al, Nature Immunol, 2019), and epigenetic regulators (Ji Y. et al, Nature Commun, 2019) to microRNAs (Ji Y. et al, Proc Natl Acad Sci USA, 2015), and metabolic pathways (Sukumar et al, J Clin Invest 2013, Hermans D. et al, Proc Natl Acad Sci USA, 2020). More recently, our division has embarked on pioneering endeavors to reprogram T-cell function by leveraging intercellular communication mechanisms such as exosome-mediated delivery of microRNAs and nanotube-mediated organelle trafficking. These innovative approaches hold the promise of further enhancing T-cell therapeutic potential. 02 | Preclinical Development Program Building upon the insights gained from our Basis Discovery Program, the Preclinical Development Program serves as a bridge between benchside discoveries and bedside applications. We translate our reprogramming strategies into practical interventions by implementing them in human T cells. Through rigorous evaluation in humanized xenograft models, we gain crucial insights into the in vivo effectiveness of these approaches (Gattinoni L. et al, Nature Med, 2011). 03 | Clinical Cell Manufacturing Program The Clinical Cell Manufacturing Program is dedicated to taking our groundbreaking discoveries to the next level—direct application in early phase-I/II clinical trials. To achieve this, we develop Good Manufacturing Practice (GMP)-grade cell-processing protocols and standard operating procedures. Our aim is to ensure the safety and efficacy of these novel therapies, laying the foundation for their use in clinical settings (Sabatino M. et al, Blood, 2016). One major focus for our investigation is the development of immunotherapies based on the adoptive transfer of T memory stem cells (Tscm). A clinical-grade process for the manufacturing of CAR-modified Tscm has been successfully developed, and this innovative platform will serve as a launch pad for the next wave of adoptive Tscm-based immunotherapies (Gattinoni L. et al, Nature Med, 2017). Publications Visit the complete list of our Research Division’s publications on Google Scholar: https://scholar.google.com/citations?user=qL6ESpUAAAAJ&hl=en Here is a selection of the most important publications from the last few years: Schelker RC, Fioravanti J, Mastrogiovanni F, Baldwin JG, Rana N, Li P, Chen P, Vadász T, Spolski R, Heuser-Loy C, Slavkovic-Lukic D, Noronha P, Damiano G, Raccosta L, Maggioni D, Pullugula S, Lin JX, Oh J, Grandinetti P, Lecce M, Hesse L, Kocks E, Martín-Santos A, Gebhard C, Telford WG, Ji Y, Restifo NP, Russo V, Rehli M, Herr W, Leonard WJ, Gattinoni L. LIM-domain-only 4 (LMO4) enhances CD8+ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling. Signal Transduct Target Ther. 2024 Aug 9;9(1):199. doi: 10.1038/s41392-024-01915-z. PMID: 39117617 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. Nat Immunol. 2019 Mar;20(3):337-349. doi: 10.1038/s41590-018-0311-z. PMID: 30778251 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 May 14;10(1):2157. doi: 10.1038/s41467-019-09882-8. PMID: 31089138 Gattinoni L, Speiser DE, Lichterfeld M, Bonini C. T memory stem cells in health and disease. Nat Med. 2017 Jan 6;23(1):18-27. doi: 10.1038/nm.4241. PMID: 28060797 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 Jul 28;128(4):519-28. doi: 10.1182/blood-2015-11-683847. PMID: 27226436 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 U S A. 2015 Jan 13;112(2):476-81. doi: 10.1073/pnas.1422916112. PMID: 25548153 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 Sep 16. doi: 10.1172/JCI69589. PMID: 24091329 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. Nat Med. 2011 Sep 18;17(10):1290-7. doi: 10.1038/nm.2446. PMID: 21926977 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. Nat Immunol. 2011 Nov 6;12(12):1230-7. doi: 10.1038/ni.2153. PMID: 22057288 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. Nat Med. 2009 Jul;15(7):808-13. doi: 10.1038/nm.1982. PMID: 19525962 Translation We are dedicated to developing innovative cell-therapy initiatives for the treatment of patients with advanced cancer. Late-phase development projects include: Collaboration with Miltenyi Biotec Together, we are developing a cGMP-compliant, semi-automated manufacturing platform for the generation of CD22/CD19-bispecific CD8+ Tscm cells. The cellular product developed will be tested in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Collaboration with Poseida Therapeutics Together, we are developing a manufacturing platform for the generation of NY-ESO-1-TCR redirected Tscm cells, functionally empowered through the overexpression of human miR-155 SNP rs377265631. The cellular product developed will be tested in patients with relapsed or refractory sarcoma. Collaborations We participate in several national and international research consortia: EIC-Pathfinder T-FITNESS: Fine-Tuning Networks of Exhaustion by Synthetic Sensors This EU consortium aims to generate antitumor T cells which are refractory to terminal differentiation and dysfunction. This ambitious goal will be pursued through the development of innovative microRNA-based synthetic logic circuits capable of rewiring the transcriptional programs driving T-cell exhaustion. The leadership and coordination of this project are centered at the LIT, where our primary focus lies in comprehensively characterizing the phenotype, function, and metabolic profiles of T cells that have undergone reprogramming using T-FITNESS technology. https://www.t-fitness-horizon.eu/ EIC Pathfinder INCITE: Immune Niches for Cancer Immunotherapy Enhancement This EU consortium seeks to develop a 3D-printed immune niche microenvironment for the generation and expansion of tumor-specific stem cell memory T cells. Within this consortium, we are responsible for functionally evaluating human CAR T cells generated within INCITE artificial immune niches and comparing them with those manufactured with the current technology. https://incite.eu.com/ CRC/ TR221 – GvHGvL The focus of this national consortium is to improve the safety and efficacy of allogeneic stem cell transplantation by developing innovative strategies to modulate graft-versus-host and graft-versus-leukemia immune responses. Our role in this Collaborative Research Center is to investigate whether donor-derived CAR-modified CD8+ T memory stem cells provide a safer and more effective platform to treat human B-cell malignancies which have relapsed after allogeneic stem cell transplantation. https://www.gvhgvl.de/ Funding We would like to thank the funding agencies who support our work: 2024-2030: German Cancer Aid (DKH), Cancer Therapy Studies A phase I safety, dose-finding, and feasibility trial of LIT-TSCM-CART-CD22/19 in patients with relapsed or refractory aggressive B cell Non-Hodgkin lymphoma. 2022–2027: German Research Foundation (DFG), Reinhart Koselleck Project Reprogramming CD8+ T-cell metabolism and fate by MSC mitochondrial transfer. 2022–2026: EIC Pathfinder Challenges 2021 Fine-tuning T-cell networks in exhaustion using synthetic sensors. 2021–2025: German Research Foundation (DFG), CRC/ TR221, Project A07 Enhancing graft-versus-leukemia responses by donor-derived CAR-modified CD8+ T memory stem cells. 2021–2025: EIC Pathfinder Immune niches for cancer immunotherapy enhancement. Team & Lab Life Prof. Luca Gattinoni Head of Research Division | Functional Immune Cell Modulation Tel: +49 941 944–38131 Email: luca.gattinoni@lit.eu Katrin Zehenter Team Assistant Tel: +49 941 944–38132 Email: katrin.zehenter@ukr.de Research team Prof. Luca Gattinoni Head of Research Division | Functional Immune Cell Modulation Dr. Roland Schelker Postdoctoral Scientist Dr. Dragana Slavkovic-Lukic Senior Scientist Dr. Christoph Heuser-Loy Senior Scientist Dr. Jeremy Baldwin Postdoctoral Scientist Dr. Esen Sayin Postdoctoral Scientist Dr. Maka Malania Project Manager Nisha Rana Bioinformatician Gabriele Inchingolo PhD Student Timea Vadász PhD Student Dr. Caio Silveira Postdoctoral Scientist Fabio Mastrogiovanni Research Technician Pedro Noronha Research Technician Azucena Martin Research Technician Dr. Asia Majidi Postdoctoral Scientist Previous Next Close Dr. Roland Schelker Postdoctoral Scientist Functional Immune Cell Modulation Tel: +49 941 944-18139 Email: Roland.Schelker@ukr.de Dr. Roland Schelker received his M.D. from the University of Cluj-Napoca in 2009. Since 2009 he has been working as a Resident Physician (2009-2018) and as a Specialist Physician (2018-present) in Internal Medicine, Hematology, and Oncology at the Department of Hematology and Medical Oncology, University Hospital Regensburg. During 2019-2021 he was a DFG-funded Visiting Research Fellow at the National Institutes of Health (Bethesda, USA), in the laboratories of Luca Gattinoni (Experimental Transplantation and Immunotherapy Branch; National Cancer Institute) and Warren Leonard (Laboratory of Molecular Immunology; National Heart, Lung and Blood Institute). In 2021, Dr. Schelker joined the LIT Division of Functional Immune Cell Modulation as a Postdoctoral scientist. His research interest focuses on the role of transcriptional co-regulators in CD8+ T cell stemness, memory formation, and antitumor immunity. Close Dr. Dragana Slavkovic-Lukic Senior Scientist Functional Immune Cell Modulation Tel: +49 941 944-18138 Email: Dragana.Slavkovic-Lukic@ukr.de – on maternity leave – Dr. Dragana Slavkovic Lukic received her Ph.D. degree from University of Heidelberg in 2012 with a thesis focusing on the interaction of spumaretroviruses with host cells and their potential use as gene-engineering vectors. After completing her Ph.D. studies, she worked as a postdoctoral scientist at Würzburg University Hospital where she gained valuable knowledge on translation research by working on T cell-engaging bispecific antibodies and TCR-redirected T cells. She joined LIT in 2020 as the head of the preclinical development and clinical cell manufacturing programs of the Division of Functional Cell Immune Modulation. Close Dr. Christoph Heuser-Loy Senior Scientist Functional Immune Cell Modulation Tel: +49 941 944-18138 Email: christoph.heuser@ukr.de Dr. Christoph Heuser is a Senior Scientist in the Division for Functional Immune Cell Modulation headed by Prof. Dr. Luca Gattinoni. From 2006 to 2011, Christoph studied Molecular Biomedicine at the University of Bonn where he also obtained his Ph.D. at the Institute of Molecular Medicine and Experimental Immunology (supervisor: Prof. Dr. Christian Kurts). Funded by the German Academic Scholarship Foundation, he investigated how Dendritic Cells initiate innate and adaptive immune responses against infections and upon tumor vaccination. Moreover, he studied the timing of stimulatory as well as regulatory interactions controlling T cell responses using genetic and pharmacological tools. In 2018, Christoph moved to the Center for Translational Cancer Research of the Technical University of Munich (TranslaTUM) where he worked at characterizing human tissue-resident memory T cells by single-cell technologies. Christoph joined the LIT Division of Functional Immune Cell Modulation in 2021 to contribute to the understanding of stemness in memory T cells. His goal is to discover opportunities for manipulating the cells’ signaling networks to ultimately advance adoptive cell therapies against cancer. Close Dr. Jeremy Baldwin Postdoctoral Scientist Functional Immune Cell Modulation Tel: +49 941 944-18139 Email: Jeremy.Baldwin@ukr.de Dr. Jeremy Baldwin is an early career research fellow specializing in the fields of immunology, vaccine research, cancer immunotherapies, and tissue engineering. In 2014, Dr. Baldwin was awarded an ANZ board Trustee fellowship to undertake a Ph.D. in Cell and Molecular Biology at the Queensland University of Technology. During his Ph.D. studies, he also completed a Master of Research and Development Management as part of the Australian Government’s Commercialization Training Scheme to train the next generation of entrepreneurial scientists. Other notable work experiences prior to the conferral of his Ph.D. include an internship at Harvard University to study the processes of research translation, an international research training program at the Tropical Disease Institute, Ecuador, and traveling to Antarctica as part of a youth expedition to raise awareness for renewable energies and climate change. Following successful defense of his Ph.D. thesis, Dr. Baldwin was awarded a Fulbright Future Fellowship, Endeavour Research Fellowship and Sir Winston Churchill fellowship to continue his post-doctoral training in immunology. Dr. Baldwin joined the LIT Division of Functional Immune Cell Modulation in 2021. His current research interest focuses on metabolically reprogram CD8+ T cells and its application in cancer immunotherapies. Close Dr. Esen Sayin Postdoctoral Scientist Functional Immune Cell Modulation Tel: +49 941 944-18134 Email: Esen.Sayin@ukr.de Dr. Sayin received her Ph.D. in Biotechnology from the Middle East Technical University (Turkey) in 2017 with a thesis focused on understanding the effects of chemical and physical microenvironmental cues on the mechanical properties of bone tissue-engineered artificial matrices. In 2015 she worked as a visiting research scholar at University College London (UK) to study the oxygen-limited niches within tissue-engineered bones. Upon completion of her doctorate research, Dr. Sayin received the Julia Polak European Doctorate Award from the European Society for Biomaterials. Since November 2023, Dr. Sayin has been a postdoctoral scientist in the Division of Functional Immune Cell Modulation directed by Prof. Luca Gattinoni. She works on the EIC-funded project INCITE to develop a 3D-printed immune niche microenvironment for the generation and expansion of tumor-specific stem cell memory T cells. Close Dr. Maka Malania Project Manager Functional Immune Cell Modulation Tel: +49 941 944-18134 Email: Maka.Malania@ur.de Maka Malania holds a Ph.D. degree in Physiology with an emphasis on Neuroscience. She has over 15 years of experience as a research scientist in world-class institutions and intensive training in scientific project monitoring and management process. Maka Malania joined the LIT Division of Functional Immune Modulation as a Project Manager in 2022. She coordinates the administrative and financial management efforts in EU-funded projects. Close Nisha Rana Bioinformatician Functional Immune Cell Modulation Tel: +49 941 944-18134 Email: Nisha.Rana@ukr.de Nisha Rana holds a Master’s degree in Bioinformatics from Hans Raj Mahila Maha Vidyalaya in Jalandhar, India. Before moving to Germany, Nisha worked in the industry for six years as Bioinformatics Analyst at Genotypic Technology and later at Sandor Specialty Diagnostics. In 2019, she joined the Max Planck Institute of Immunobiology and Epigenetics in Freiburg to support the bioinformatics activities in the laboratory of Dr. Erika Pearce. In 2021, Nisha moved to Dr. Bengsch’s group at the University Hospital in Freiburg where she acquired skills in analyzing Cy-Tof and IMC. Since July 2023, Nisha has been a Bioinformatician within the LIT Division of Functional Immune Cell Modulation. Nisha’s expertise lies in working with various types of next-generation sequencing data, with a primary focus on RNA-Seq, ChIP-Seq, ATAC-Seq, scRNA-Seq, and more. She utilizes a range of software, databases, and scripting languages to extract valuable insights from the complex realm of genetic data. Close Gabriele Inchingolo PhD Student Functional Immune Cell Modulation Tel: +49 941 944-18134 Email: Gabriele.Inchingolo@ukr.de Gabriele Inchingolo is currently a Ph.D. student in Division for Functional Immune Cell Modulation. Gabriele graduated from the University of Bari in Medical Biotechnology and Molecular Medicine with honors. He has an academic and industrial background. His research interest is in the area of immuno-oncology and lymphocyte biology, with a particular focus on ex vivo T-cell engineering for cancer immunotherapy applications, T cell exhaustion, differentiation and memory formation. Gabriele‘s thesis project involves immunomonitoring of patients enrolled in Phase I clinical trial of anti-CD19 CAR TSCM cells against B cells malignancies. Close Timea Vadász PhD Student Functional Immune Cell Modulation Tel: +49 941 944-18138 Email: Selina-Timea.Vadasz@ukr.de Timea Vadász successfully completed her bachelor’s degree in Molecular Medicine at Ulm University in 2020, during which she gained first insight into molecular immunology and discovered her deep interest in T cell biology. During her undergraduate studies, Timea worked at the Institute for Transfusion Medicine on the topic “Production of an AK2-deficient human cell line as a model system for pathophysiological studies of reticular dysgenesis”. In October 2020, she started studying for a master’s degree in Molecular Medicine at the University of Regensburg to further specialize in the field of immunology. Timea joined the research group of Professor Gattinoni in January 2022, as an intern, continued her research in the same group and culminated her master’s thesis titled “Enhancing CD8+ T cell antitumor response through Rbbp4/7 mediated epigenetic reprogramming”. Timea is currently a Ph.D. student and her thesis project focuses on “Reprogramming the Tumor Milieu by T cell-mediated Exosomal miRNA Delivery”. Her main goal is to uncover novel pathways that can be therapeutically exploited to overcome current hurdles facing cancer immunotherapies. Close Dr. Caio Silveira Postdoctoral Scientist Functional Immune Cell Modulation Tel: +49 941 944–38134 Email: Caio.Silveira@ukr.de Dr. Caio Silveira received his Ph.D. from the University of Sao Paulo in 2019 with a thesis focused on the development of novel strategies to reprogram the tumor microenvironment in cervical cancer under the supervision of Dr. Ana Paula Lepique. Caio worked then as an analyst in cell therapy at Hospital Israelita Albert Einstein (2019-2020), where he acquired extensive experience in the GMP manufacturing of TILs and virus-specific T cells. From 2020 to 2023 he was a postdoctoral scientist at the Advanced Cell Therapy Laboratory at the University of São Paulo/Fundação Hemocentro de Ribeirão Preto, working on the development of new vectors for the production of CAR T cells, under the scientific supervision of Dr. Renato Cunha. In October 2023 Dr. Silveira joined the Division for Functional Immune Cell Modulation at LIT. In Dr. Luca Gattinoni’s group, Caio works on the EIC-funded T-FITNESS project to overcome major barriers to successful cell therapies and to foster his academic career. Close Fabio Mastrogiovanni Research Technician Functional Immune Cell Modulation Tel: +49 941 944-18137 Email: Fabio.Mastrogiovanni@ukr.de Fabio Mastrogiovanni received an M.Sc. degree in Biology from the Naples University Federico II and is FELASA accredited since 2021. Before joining the LIT, he worked as a research technician at DZNE -German Institute for Neurodegenerative Diseases- and at TUM – Technical University of Munich. Since 2019, he has been a research assistant in the Division of Functional Immune Modulation. He is the technical coordinator of the ZTL – Animal Experimentation Area – and is also responsible for managing and developing various experimental procedures. Close Pedro Noronha Research Technician Functional Immune Cell Modulation Tel: +49 941 944-18134 Email: Pedro.Noronha@ukr.de Pedro Noronha received a B.Sc. in Biomedical Engineering from the Universidade Católica Portuguesa in 2013. He joined the LIT Division of Functional Immune Cell Modulation in 2021 after working for two years as Research Technician at the ImmunoSurgery Lab at the Champalimaud Foundation in Lisbon. His interests rely on adoptive cell therapy, and on the optimization of autologous or allogenic immune cell therapy products by using engineering and biotechnology techniques. Close Azucena Martin Research Technician Functional Immune Cell Modulation Tel: +49 941 944-18135 Azucena Martín holds a B.Sc. degree. She provided technical support to several groups actively involved in immunology and translational medicine research in both UK and Germany, before joining the LIT Division of Functional Immune Cell Modulation in 2019. Azucena currently manages the running of the laboratory and supports research activities across the group’s different projects. Close Dr. Asia Majidi Postdoctoral Scientist Functional Immune Cell Modulation Tel: +49 941 944-18138 Email: Asia.Majidi@ukr.de Lab Life There is life outside the laboratory: The Leibniz Institute places great value on our scientists developing the team spirit both in and out of work. Here are the photos to prove it! 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