Reshaping undesired Inflammation in challenged Tissue Homeostasis by Next-Generation regulatory T cell (Treg) Approaches – from Advanced Technology Developments to First-in-Human Trials

Project Information

RESHAPE

Grant agreement ID: 825392

DOI

10.3030/825392

Project closed

EC signature date 21 November 2018

Start date 1 January 2019

End date 31 December 2024

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 13 137 396,25

EU contribution

€ 13 137 396,25

Coordinated by

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Documents, reports (16)

Humanised vascularized skin Tx

Evaluation of 2 best-in-class Treg in the new humanised vascularised skin Tx model

Position paper CAR-Treg

Position /Viewpoint paper on CAR-Treg generation

RNAseq, TCRseq, Methylation report

All preseleted Treg products analysed

Position paper next generation Treg

Position paper on challenges and opportunities of nextgeneration Treg approaches

Final statement on IL-tgTreg

Final statement to the utility of IL-2tg Treg (WP1-3)

Final statement on off-the-shelf Treg

Final statement to the utility of off-the-shelf allogeneic Treg

Final statement on non-viral gene del.

Final statement to the utility of virusfree gene transfer methods for Treg

Cytometry report

All preseleted Treg products analysed

Final statement on epigenetic Treg

Final statement to the utility of epigenetically stabilised Treg

PoC rejection model on-chip

Evaluation of kidney rejection on-chip and the effects of Treg treatmentPoC

DigiWest/Luminex report

All preseleted Treg products analysed

Position paper Crispr/Cas in Tcells

Positon paper on challenges for using CRISPRCas9 modified T cells

Final statement on SPR Treg

Final statement to the utility of SPR Treg

GMP protocol for at least one tissue-specific Treg
Final statement on metabolic Treg

Final statement to the utility of mitochondrial reprogramming of Treg

Final statement on Cas9 TCR-Treg

Final statement to the utility of Cas9-specific TCR-Treg

Websites, patent fillings, videos etc. (1)

Launching website

Publications

Peer reviewed articles (32)

Effector memory–type regulatory T cells display phenotypic and functional instability

Author(s): Désirée Jacqueline Wendering, Leila Amini, Stephan Schlickeiser, Martí Farrera-Sal, Sarah Schulenberg, Lena Peter, Marco Mai, Tino Vollmer, Weijie Du, Maik Stein, Frederik Hamm, Alisier Malard, Carla Castro, Mingxing Yang, Ramon Ranka, Timo Rückert, Pawel Durek, Frederik Heinrich, Gilles Gasparoni, Abdulrahman Salhab, Jörn Walter, Dimitrios Laurin Wagner, Mir-Farzin Mashreghi, Sybille Landweh
Published in: Science Advances, Issue 10, 2024, ISSN 2375-2548
Publisher: American Association for the Advancement of Science
DOI: 10.1126/sciadv.adn3470

Strong Expansion of Human Regulatory T Cells for Adoptive Cell Therapy Results in Epigenetic Changes Which May Impact Their Survival and Function

Author(s): Kristy Ou, Dania Hamo, Anne Schulze, Andy Roemhild, Daniel Kaiser, Gilles Gasparoni, Abdulrahman Salhab, Ghazaleh Zarrinrad, Leila Amini, Stephan Schlickeiser, Mathias Streitz, Jörn Walter, Hans-Dieter Volk, Michael Schmueck-Henneresse, Petra Reinke, Julia K Polansky
Published in: Frontiers in Cell and Developmental Biology, Issue 751590, 2021, ISSN 2296-634X
Publisher: Frontiers
DOI: 10.3389/fcell.2021.751590

Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial

Author(s): Andy Roemhild, Natalie Maureen Otto, Guido Moll, Mohamed Abou-El-Enein, Daniel Kaiser, Gantuja Bold, Thomas Schachtner, Mira Choi, Robert Oellinger, Sybille Landwehr-Kenzel, Karsten Juerchott, Birgit Sawitzki, Cordula Giesler, Anett Sefrin, Carola Beier, Dimitrios Laurin Wagner, Stephan Schlickeiser, Mathias Streitz, Michael Schmueck-Henneresse, Leila Amini, Ulrik Stervbo, Nina Babel, Hans-Dieter
Published in: British Medical Journal, Issue 371, 2020, ISSN 2057-0066
Publisher: BMJ
DOI: 10.1136/bmj.m3734

Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease

Author(s): Valerie Saetzler, Tobias Riet, Andrea Schienke, Pierre Henschel, Kiara Freitag, Alexander Haake, Frank L. Heppner, Laura Elisa Buitrago-Molina, Fatih Noyan, Elmar Jaeckel, Matthias Hardtke-Wolenski
Published in: Cells, Issue 12, 2025, Page(s) 2115, ISSN 2073-4409
Publisher: https://pubmed.ncbi.nlm.nih.gov/37626926/
DOI: 10.3390/cells12162115

Advanced Therapy Medicinal Products' Translation in Europe: A Developers' Perspective

Author(s): Maja Pizevska, Jaspal Kaeda, Enrico Fritsche, Hisham Elazaly, Petra Reinke, Leila Amini
Published in: Frontiers in Medicine, Issue 757647, 2022, ISSN 2296-858X
Publisher: Frontiers
DOI: 10.3389/fmed.2022.757647

Matching or genetic engineering of HLA Class I and II facilitates successful allogeneic ‘off-the-shelf’ regulatory T cell therapy

Author(s): Oliver McCallion, Weijie Du, Viktor Glaser, Kate Milward, Clemens Franke, Jonas Kath, Mikhail Valkov, Mingxing Yang, Annette Künkele, Julia K. Polansky, Michael Schmueck-Henneresse, Hans-Dieter Volk, Petra Reinke, Dimitrios L. Wagner, Joanna Hester, Fadi Issa
Published in: -, 2023, ISSN 2692-8205
Publisher: cold spring harbor Laboratory
DOI: 10.1101/2023.08.06.551956

Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?

Author(s): Matthias Hardtke-Wolenski, Sybille Landwehr-Kenzel
Published in: Molecular and Cellular Pediatrics, Issue 11, 2024, ISSN 2194-7791
Publisher: springer
DOI: 10.1186/s40348-024-00176-8

Freezing Medium Containing 5% DMSO Enhances the Cell Viability and Recovery Rate After Cryopreservation of Regulatory T Cell Products ex vivo and in vivo

Author(s): Daniel Kaiser, Natalie Maureen Otto, Oliver McCallion, Henrike Hoffmann, Ghazaleh Zarrinrad, Maik Stein, Carola Beier, Isabell Matz, Marleen Herschel, Joanna Hester, Guido Moll, Fadi Issa, Petra Reinke, Andy Roemhild
Published in: Frontiers in Cell and Developmental Biology, Issue 750286, 2021, ISSN 2296-634X
Publisher: Frontiers
DOI: 10.3389/fcell.2021.750286

Immune Monitoring for Advanced Cell Therapy Trials in Transplantation: Which Assays and When?

Author(s): Helen L. Stark, Hayson C. Wang, Jasmina Kuburic, Alaa Alzhrani, Joanna Hester and Fadi Issa
Published in: Frontiers in Immunology, Issue 664244, 2021, ISSN 1664-3224
Publisher: Frontiers
DOI: 10.3389/fimmu.2021.664244

Long-term in vitro maintenance of plasma cells in a hydrogel-enclosed human bone marrow microphysiological 3D model system

Author(s): Stefania Martini, Norman Michael Drzeniek, Regina Stark, Matthias Reiner Kollert, Weijie Du, Simon Reinke, Melanie Ort, Sebastian Hardt, Iuliia Kotko, Jonas Kath, Stephan Schlickeiser, Sven Geißler, Dimitrios Laurin Wagner, Anna-Catharina Krebs, Hans-Dieter Volk
Published in: Biofabrication, Issue 16, 2024, Page(s) 045005, ISSN 1758-5082
Publisher: IOS Press
DOI: 10.1088/1758-5090/ad5dfe

Cyclosporine A but Not Corticosteroids Support Efficacy of Ex Vivo Expanded, Adoptively Transferred Human Tregs in GvHD

Author(s): Sybille Landwehr-Kenzel, Anne Zobel, Isabela Schmitt-Knosalla, Anne Forke, Henrike Hoffmann, Michael Schmueck-Henneresse, Robert Klopfleisch, Hans-Dieter Volk, Petra Reinke
Published in: Frontiers in Immunology, Issue 716629, 2021, ISSN 1664-3224
Publisher: Frontiers
DOI: 10.3389/fimmu.2021.716629

Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer

Author(s): Weijie Du, Fatih Noyan, Oliver McCallion, Vanessa Drosdek, Jonas Kath, Viktor Glaser, Carla Fuster-Garcia, Mingxing Yang, Maik Stein, Clemens Franke, Yaolin Pu, Olaf Weber, Julia K. Polansky, Toni Cathomen, Elmar Jaeckel, Joanna Hester, Fadi Issa, Hans-Dieter Volk, Michael Schmueck-Henneresse, Petra Reinke, Dimitrios L. Wagner
Published in: Molecular Therapy, 2025, ISSN 1525-0016
Publisher: Nature Publishing Group
DOI: 10.1016/j.ymthe.2025.01.045

Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants

Author(s): Oliver McCallion, Amy R. Cross, Matthew O. Brook, Conor Hennessy, Ricardo Ferreira, Dominik Trzupek, William R. Mulley, Sandeep Kumar, Maria Soares, Ian S. Roberts, Peter J. Friend, Giovanna Lombardi, Kathryn J. Wood, Paul N. Harden, Joanna Hester, Fadi Issa
Published in: Med, 2024, Page(s) 100561, ISSN 2666-6340
Publisher: Cell press
DOI: 10.1016/j.medj.2024.11.014

CTGCT, Centre of Excellence for the Technologies of Gene and Cell Therapy: Collaborative translation of scientific discoveries into advanced treatments for neurological rare genetic diseases and cancer

Author(s): Darja Marolt Presen, Duško Lainšček, Jane Kinghorn, Zsolt Sebestyen, Jurgen Kuball, Leila Amini, Petra Reinke, Anke Fuchs, Roman Jerala, Mojca Benčina
Published in: Computational and Structural Biotechnology Journal, Issue 27, 2024, Page(s) 10-16, ISSN 2001-0370
Publisher: Elsevier
DOI: 10.1016/j.csbj.2024.11.051

Integration of <i>ζ</i>-deficient CARs into the <i>CD3</i> <i>ζ</i> gene conveys potent cytotoxicity in T and NK cells

Author(s): Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E. Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-el-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios L. Wag
Published in: Blood, Issue 143, 2024, Page(s) 2599-2611, ISSN 0006-4971
Publisher: American Society of Hematology
DOI: 10.1182/blood.2023020973

Recent advances in our understanding of the allograft response

Author(s): Conor Hennessy , Guido Lewik , Amy Cross , Joanna Hester , Fadi Issa
Published in: Faculty Opinions, Issue 10:21, 2021, ISSN 2634-0836
Publisher: Faculty opinions
DOI: 10.12703/r/10-21

Toward an Optimized Process for Clinical Manufacturing of CAR-Treg Cell Therapy

Author(s): Enrico Fritsche, Hans-Dieter Volk, Petra Reinke, Mohamed Abou-El-Enein
Published in: Trends in Biotechnology, 2020, Page(s) 1-13, ISSN 0167-7799
Publisher: Elsevier BV
DOI: 10.1016/j.tibtech.2019.12.009

Future prospects for CD8 + regulatory T cells in immune tolerance

Author(s): Léa Flippe, Séverine Bézie, Ignacio Anegon, Carole Guillonneau
Published in: Immunological Reviews, Issue 292/1, 2019, Page(s) 209-224, ISSN 0105-2896
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/imr.12812

Post-marketing safety and efficacy surveillance of cell and gene therapies in the EU: A critical review

Author(s): Enrico Fritsche, Magdi Elsallab, Michaela Schaden, Spencer Phillips Hey, Mohamed Abou-El-Enein
Published in: Cell and Gene Therapy Insights, Issue 5/11, 2019, Page(s) 1505-1521, ISSN 2059-7800
Publisher: BIOINSIGHTS PUBLISHING
DOI: 10.18609/cgti.2019.156

In Vivo Analysis of Human Immune Responses in Immunodeficient Rats

Author(s): Séverine Ménoret, Laure-Hélène Ouisse, Laurent Tesson, Séverine Remy, Claire Usal, Aude Guiffes, Vanessa Chenouard, Pierre-Joseph Royer, Gwenaelle Evanno, Bernard Vanhove, Eliane Piaggio, Ignacio Anegon
Published in: Transplantation, Issue 104/4, 2020, Page(s) 715-723, ISSN 0041-1337
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/tp.0000000000003047

Humanization of Immunodeficient Animals for the Modeling of Transplantation, Graft Versus Host Disease and Regenerative Medicine

Author(s): George Adigbli, Séverine Ménoret, Amy R. Cross, Joanna Hester, Fadi Issa, Ignacio Anegon
Published in: Transplantation, Issue Publish Ahead of Print, 2020, ISSN 0041-1337
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/tp.0000000000003177

New frontiers: cellular immunotherapy beyond cancer

Author(s): Matthew Brook, Joanna Hester, Fadi Issa
Published in: Cell and Gene Therapy Insights, Issue 5/12, 2019, Page(s) 1229-1236, ISSN 2059-7800
Publisher: BIOINSIGHTS
DOI: 10.18609/cgti.2019.163

Non-viral TRAC-knocked-in CD19KICAR-T and gp350KICAR-T cells tested against Burkitt lymphomas with type 1 or 2 EBV infection: In vivo cellular dynamics and potency

Author(s): Tobias Braun, Alina Pruene, Milita Darguzyte, Alexander F. vom Stein, Phuong-Hien Nguyen, Dimitrios L. Wagner, Jonas Kath, Alicia Roig-Merino, Michael Heuser, Lucas L. Riehm, Andreas Schneider, Sabine Awerkiew, Steven R. Talbot, André Bleich, Constanca Figueiredo, Martin Bornhäuser, Renata Stripecke
Published in: Frontiers in Immunology, Issue 14, 2023, ISSN 1664-3224
Publisher: Frontiers Media S.A.
DOI: 10.3389/fimmu.2023.1086433

Super-Treg: Toward a New Era of Adoptive Treg Therapy Enabled by Genetic Modifications

Author(s): Leila Amini, Jenny Greig, Michael Schmueck-Henneresse, Hans-Dieter Volk, Séverine Bézie, Petra Reinke, Carole Guillonneau, Dimitrios L Wagner, Ignacio Anegon
Published in: Frontiers in Immunology, Issue 611638, 2021, ISSN 1664-3224
Publisher: Frontiers
DOI: 10.3389/fimmu.2020.611638

Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy?

Author(s): Dimitrios Laurin Wagner, Lena Peter, Michael Schmueck-Henneresse
Published in: Gene Therapy, 2021, Page(s) 549–559, ISSN 0969-7128
Publisher: Nature Publishing Group
DOI: 10.1038/s41434-021-00232-2

Chimeric Antigen Receptors and Regulatory T Cells: The Potential for HLA-Specific Immunosuppression in Transplantation

Author(s): Sabrina Wright, Conor Hennessy,Joanna Hester, Fadi Issa
Published in: Engineering, 2021, ISSN 2095-8099
Publisher: Elsevier Ltd
DOI: 10.1016/j.eng.2021.10.018

Gene editing of<i>CD3 epsilon</i>gene to redirect regulatory T cells for adoptive T cell transfer

Author(s): Weijie Du, Fatih Noyan, Oliver McCallion, Vanessa Drosdek, Jonas Kath, Viktor Glaser, Carla Fuster-Garcia, Mingxing Yang, Maik Stein, Olaf Weber, Julia K. Polansky, Toni Cathomen, Elmar Jaeckel, Joanna Hester, Fadi Issa, Hans-Dieter Volk, Michael Schmueck-Henneresse, Petra Reinke, Dimitrios L. Wagner
Published in: Biorxiv, 2024, ISSN 2692-8205
Publisher: cold spring harbor Laboratory
DOI: 10.1101/2024.03.18.584896

Genetic engineering of human and mouse CD4+ and CD8+ Tregs using lentiviral vectors encoding chimeric antigen receptors

Author(s): Nadège Vimond, Juliette Lasselin, Ignacio Anegon, Carole Guillonneau, Séverine Bézie
Published in: Molecular Therapy - Methods & Clinical Development, Issue 20, 2020, Page(s) 69-85, ISSN 2329-0501
Publisher: Elsevier
DOI: 10.1016/j.omtm.2020.11.008

Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis

Author(s): Laura Elisa Buitrago-Molina, Julia Pietrek, Fatih Noyan, Jerome Schlue, Michael P. Manns, Heiner Wedemeyer, Matthias Hardtke-Wolenski, Elmar Jaeckel
Published in: Journal of Autoimmunity, Issue 117, 2021, Page(s) 102591, ISSN 0896-8411
Publisher: Academic Press
DOI: 10.1016/j.jaut.2020.102591

Targeted De-Methylation of the FOXP3-TSDR Is Sufficient to Induce Physiological FOXP3 Expression but Not a Functional Treg Phenotype

Author(s): Christopher Kressler, Gilles Gasparoni, Karl Nordström, Dania Hamo, Abdulrahman Salhab, Christoforos Dimitropoulos, Sascha Tierling, Petra Reinke, Hans-Dieter Volk, Jörn Walter, Alf Hamann and Julia K. Polansky
Published in: Frontiers in Immunology, Issue 609891, 2021, ISSN 1664-3224
Publisher: Frontiers
DOI: 10.3389/fimmu.2020.609891

Low-Dose Interleukin-2 Therapy: Fine-tuning Treg in Solid Organ Transplantation?

Author(s): Leila Amini, Jaspal Kaeda, Olaf Weber, Petra Reinke
Published in: Transplantation, 2024, ISSN 0041-1337
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/tp.0000000000004866

Identification, selection, and expansion of non-gene modified alloantigen-reactive Tregs for clinical therapeutic use

Author(s): Alaa Alzhrani , Matthew Bottomley , Kathryn Wood , Joanna Hester , Fadi Issa
Published in: Cellular Immunology, Issue 357:104214, 2020, ISSN 1090-2163
Publisher: Elsevier
DOI: 10.1016/j.cellimm.2020.104214

Non-peer reviewed articles (2)

TCAIM controls effector T cell generation by preventing Mitochondria-Endoplasmic Reticulum Contact Site-initiated Cholesterol Biosynthesis

Author(s): Christina Iwert, Julia Stein, Christine Appelt, Katrin Vogt, Roman Josef Rainer, Katja Tummler, Kerstin Mühle, Katarina Stanko, Julia Schumann, Doreen Uebe, Karsten Jürchott, Jan Lisec, Katharina Janek, Christoph Gille, Kathrin Textoris-Taube, Somesh Sai, Ansgar Petersen, Anja A. Kühl, Edda Klipp, Christian Meisel, Birgit Sawitzki
Published in: bioRxiv, 2021, ISSN 2692-8205
Publisher: Cold Sping Harbor Laboratory
DOI: 10.1101/2021.04.20.440500

Fast, efficient and virus-free generation of TRAC-replaced CAR T cells

Author(s): Jonas Kath, Weijie Du, Bernice Thommandru, Rolf Turk, Leila Amini, Maik Stein, Tatiana Zittel, Stefania Martini, Lennard Ostendorf, Andreas Wilhelm, Levent Akyüz, Armin Rehm, Uta E. Höpken, Axel Pruß, Annette Künkele, Ashley M. Jacobi, Hans-Dieter Volk, Michael SchmueckHenneresse, Petra Reinke, Dimitrios L. Wagner
Published in: bioRxiv, 2021, ISSN 2692-8205
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2021.02.14.431017