The ReSHAPE project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement n. 825392

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ReSHAPE aims at transforming the treatment of patients suffering from undesired Immunity/Inflammation (Allotransplantation, Autoimmunity, Hyperinflammation, and Regenerative Medicine, including Gene Therapy) who presently have limited curative treatment options by applying next-generation Treg approaches that overcome the limitations of 1st generation Treg product developments.

ReSHAPE will use Treg therapy as a very promising new tool for reshaping undesired inflammation/immunity applicable in many disease situations with high unmet medical need which can be used as role model for any approach of next-generation ATMP (Advanced Therapy Medicinal Product).

ReSHAPE will create different platforms, such as a knowledge platform based on previous work of the consortium but also on applying new technology and medical approaches for improved Treg therapies, including next-generation Treg product platform, novel preclinical testing platform, clinical development and clinical trial platform, including accompanying biomarker studies, as well as a HTA/exploitation platform. The platforms comprise the components and expertise necessary to create a solid foundation on which to build new therapeutic Treg approaches and cell products beyond Treg and aim at overcoming particular development bottlenecks.

The ReSHAPE consortium will develop next-generation Treg products and will prove next-generation approaches in clinical trials.

ReSHAPE´s next-generation Treg therapy approaches are applicable for organ and hematopoetic stem cell transplantation and beyond in many medical indication fields, such as Autoimmunity, Hyperinflammation, and Regenerative Therapies, including Gene Therapies.

ReSHAPE´s next-generation Treg approaches will translate a significant technology progress in the advanced therapy field from early development to First-In-Human (FIH) clinical trials with a concept for moving forward further in the added value chain of ATMP implementation.




ReSHAPE Second Annual Meeting, 10-11 March 202 (online event hosted by Innovation Acta)


ReSHAPE First Annual Meeting, 23-24 January 2020 Berlin, Germany


ReSHAPE participates to RESTORE 1ATSM in Berlin

Prof. Petra Reinke project Coordinator will give the talk “Reshape immune balance by next-generation regulatory T cells”

In the programme talks of Hans Dieter Volk (Charité), Julia Polansky-Biskup (Charité), Leila Amini (Charité), Joanna Hester (UOXF)


ReSHAPE Kick Off Meeting, 07-08 February in Berlin (Germany)


ReSHAPE website online



Members of the consortium are pioneers in the development of Treg therapy from basic science to very recent encouraging First-In-Human (FIH) clinical trials of 1st generation Treg products. They have a longtrack record of collaboration, including EC-funded projects (e.g. IOT, RISET, One Study, BIO-DrIM). The first clinical trials were performed to combat organ transplant rejection and Graft-versus-Host Disease (GvHD) post allo-HSC transplantation. However, promising preclinical studies offer a broad application field of Treg therapy beyond allotransplantation.


Based on our extensive preclinical and first clinical data, we identified several opportunities for improving Treg therapy which will be addressed by ReSHAPE:

  • Redirecting antigen specificity by CAR/TCR-Treg
  • Enhanced functional stability of Treg under in vivo challenges by innovative genetic and epigenetic modifications of Treg
  • Support of Treg engraftment in vivo by particular conditioning of the recipients and/or enabling Treg to secrete their own growth factors
  • New in vitro & in vivo tools for in-depth characterisation of Treg product candidates for better standardisation of the manufacturing process and preclinical PoC studies with enhanced predictive value for derisking clinical development
  • Clinical trials accompanied by a broad portfolio of highly standardised biomarkers to better understand the complex “living” medicinal products regarding their therapy response, such as PK/PD, safety, mode-of-action, putative surrogate markers of efficacy.
  • Research to generate innovative clinical development roadmaps and early health economic assessment to support the development of business models for next level of clinical development and commercial exploration of innovations



State of Art

Dynamic tissue homeostasis is based on the crosstalk of intratissue parenchymal, stromal, and immune cells that is guided by the extracellular matrix “code” and regulated in a bi(multi)-directional way. Acute and chronic events such as trauma, ischemia/reperfusion injury, (auto/allo)-immune attack, challenge the homeostasis and result in adaptive processes, including further cellular recruitment. The fate of the tissue response is not only influenced by the strength and duration of the challenges but also by disease modifiers, such as age, malformation, metabolic disbalance.

It is becoming more and more clear that the intratissue balance of inflammation/immunity has a major impact on maintenance/restoration of tissue homeostasis by controlling the state and fate of progenitor/stem/ stromal cells and extracellular matrix dynamics.

Thymically derived FOXP3+ regulatory T cells (tTreg) constitute a unique T cell lineage that is essential for maintaining immune tolerance to self as well as innocuous environmental antigens and intratissue immune homeostasis. However, FOXP3 can also be turned on in conventional T cells with effector functions (Teff) as consequence of antigen exposure in the periphery, under both non-inflammatory and inflammatory conditions. These so-called peripheral Treg (pTreg) that involve both CD4+ and CD8+ pTreg cells, participate in the control of immunity at sites of inflammation. Both tTreg and pTreg can control inflammation/immunity by multiple mechanisms, such as i) competition with Teff for IL-2, ii) through cAMP-mediated immunosuppression, iii) adenosine production via the ectoenzymes, CD39 and CD79, iv) secretion of inhibitory cytokines (e.g. IL-10, TGF-ß, IL-33, IL-34), and v) cytolysis of Teff via granzyme/perforin-dependent mechanisms.

Diminished number and/or function of Treg, e.g. by malformation (e.g. IPEX syndrome), and disbalanced Teff/Treg ratio at the site of inflammation result in unwanted inflammation/immunity associated with autoimmunity, autoinflammation, and disturbed regeneration from trauma and ischemia/reperfusion. Consequently, agonistic targeting of Treg is a promising therapeutic option to combat undesired inflammation/immunity in a broad range of medical indications. Although in vivo Treg induction/expansion approaches, such as blocking co-stimulatory signals during antigen exposure, tolerogenic dendritic cells, tolerogenic peptide vaccination, and low-dose IL-2 show some efficacy in preclinical models and First-In-Human trials, their efficacy is limited and some adverse effects can be observed. In many preclinical models, the adoptive transfer of Treg is more effective. The recent (bio) technological advances to isolate and expand human Treg under GMP compliant conditions, now allow adoptive Treg therapy to be introduced to the clinic, opening up new opportunities.

Treg products (with or without genetic manipulation) for the adoptive transfer are regulatory categorized as Advanced Therapy Medicinal Product (ATMP). ATMP therapies are based on gene, cell or tissue-engineered products which are defined according to the terms of Regulation 1394/2007. So far, only a small number of these products have been placed on the market, not a single Treg product so far.

The ReSHAPE consortium will develop next-generation Treg products and will prove next-generation approaches in clinical trials.




The ReSHAPE consortium is coordinated by the Charité – Universitätsmedizin Berlin. The project coordinator is MD Petra Reinke, Professor of Nephrology and Transplantation within the following scientific topics: transplantation medicine, development of new diagnostic and therapeutic approaches in transplantation (non-invasive immune Biomarkers, detection and targeting of memory T cells and adoptive Teff/Treg T cell therapy) and founding director of the Berlin Center for Advanced Therapies (BeCAT) that 2017 received in a highly competitive procedure a 30 Mio € funding by the German Council of Science and Humanities.


ReSHAPE Second Annual Meeting, 10-11 March 202
pin Online event hosted by Innovation Acta

ReSHAPE First Annual Meeting, 23-24 January 2020
pin Berlin (Germany)


pdf   Meeting Agenda

ReSHAPE Kick Off Meeting, 07-08 February 2019
pin Berlin (Germany)


pdf   Meeting Agenda

pdf   List of Participants



  • 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 Volk, Petra Reinke.
    Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial.
    BMJ, 2020; 371:m3734, doi: 10.1136/bmj.m3734
    → open it on the web
  • Léa Flippe, Séverine Bézie, Ignacio Anegon, Carole Guillonneau.
    Future prospects for CD8+ regulatory T cells in immune tolerance.
    Immunological reviews, 2019, 292, 1-16, DOI: 10.1111/imr.12812
    → open it on the web
  • Séverine Ménoret, Laure-Hélène Ouisse, Laurent Tesson, Séverine Remy, Claire Usal, Aude Guiffes, Vanessa Chenouard, Pierre-Joseph Royer, Gwenaelle Evanno, Bernard Vanhove, Eliane Piaggio, and Ignacio Anegon.
    In vivo analysis of human immune responses in immunodeficient rats.
    Transplantation, 2020, 104/4, 715-723, DOI: 10.1097/tp.0000000000003047
    → open it on the web
  • George Adigbli, Séverine Ménoret, Amy R Cross, Joanna Hester, Fadi Issa, Ignacio Anegon.
    Humanization of immunodeficient animals for the modelling of transplantation, graft-versus host disease and regenerative medicine.
    Transplantation, ahead of print , DOI: 10.1097/tp.0000000000003177
    → open it on the web
  • Enrico Fritsche, Hans-Dieter, Volk Petra Reinke, Mohamed Abou-El-Enein.
    Toward an optimized process for clinical manufacturing of chimeric antigen receptor regulatory T-cell therapy (CAR-Treg) Trends in Biotechnology.
    Trends in Biotechnology, 2020, 1-13 , DOI: 10.1016/j.tibtech.2019.12.009
    → open it on the web
  • Enrico Fritsche, Magdi Elsallab, Michaela Schaden,Spencer Phillips Hey, Mohamed Abou-El-Enein.
    Post-marketing safety and efficacy surveillance of cell and gene therapies in the EU: A critical review.
    Cell & Gene Therapy Insights, 2019; 5(11), 1505–1521, DOI: 10.18609/cgti.2019.156
    → open it on the web
  • Matthew Brook, Joanna Hester, Fadi Issa.
    New frontiers: cellular immunotherapy beyond cancer.
    Cell and Gene Therapy Insights,2019, 1229-1236, DOI: 10.18609/cgti.2019.163
    → open it on the web