Immune Safety Avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies

Deliverables

Involvement of Regulatory Agencies
Summary of Patient Engagement

Summry of Patient Engagement

2nd iteration refined in vivo and in vitro model readouts IL-2 MoA

This will be the second iteration of improved model readouts that have been initially refined based upon the outcome of the imSAVAR workshop on IL-2 MoA. This will be a report that defines the refinements and describes and confirmatory work that has been done.

Preliminary irAOP - CPI Mo

Same as D2.1, but for Checkpoint inhibitors

1st iteration refined hepatoxicity in vivo models

This will be a set of models that have been initially refined based upon the outcome of the imSAVAR workshop on Checkpoint inhibitor MoA. This will be a report that defines the refinements and describes and confirmatory work that has been done.

CPI immune safety assessment research roadmap

Same as D23 but for Checkpoint inhibitors

Patient Engagement Update M60

Update of Patient Engagement M60

2nd iteration in vitro & MPS models

This is a second iteration of D2.5 which will include further refinements and possibly new models

1st iteration refined CRS in vivo models

This will be a set of models that have been initially refined based upon the outcome of the imSAVAR workshop on CAR-T/BiTE MoA. This will be a report that defines the refinements and describes and confirmatory work that has been done.

CAR-T & BITE immune safety assessment research roadmap

A document that is based upon the outcome of the imSAVAR workshops on CAR-T/BiTE immune safety assessment. It will contain a description of the highest priority irAOPs for CAR-T/BiTE MoAs, input from different stakeholders including regulators. This document will also highlight the most important areas where further research and development is needed with specific representation of what is planned for the effort in imSAVAR

1st iteration in vivo and in vitro models IL-2 Moa

This will be a set of refined in vivo models and in vitro that have been initially refined based upon the outcome of the imSAVAR workshop on IL2 MoA This will be a report that defines the refinements and describes and confirmatory work that has been done

Dissemination materials

A websiste, overview, slides, and a dynamic set of messages for use in describing and disseminating the outputs of imSAVAR and for building the stakeholder community.

TReg-IL2 immune safety assessment research roadmap

A document that is based upon the outcome of the imSAVAR workshop on TR-IL2 MoA. It will contain a description of the highest priority irAOPs for TR-IL2 MoA, and the input from different stakeholders including regulators. This document will also highlight the most important areas where further research and development is needed with specific representation of what is planned for the effort in imSAVAR

Preliminary irAOP - CAR-T & BiTE MoAs

In order to inform the attendees for the workshop and to form the basis for the assessment roadmap the preliminary irAOPs will be pathways of the most different adverse outcomes for CAR-T and BiTEs. These will be defined by the consortium members and supplemented by research and available data where possible.

Preliminary irAOP - IL2-TREG

In order to inform the attendees for the workshop and to from the basis for the assessment roadmap the preliminary irAOPs will be pathways of the most different adverse outcomes for IL2-TREG MoA. These will be define by the consortium members and supplemented by research and available data where possible.

1st iteration refined in vivo & in vitro model readouts IL-2 MoA

This will be a set of improved model readouts that have been initially refined based upon the outcome of the imSAVAR workshop on IL 2 MoA This will be a report that defines the refinements and describes and confirmatory work that has been done

3rd imSAVAR workshop

Same as 13 but for IL2 Treg MoA

1st imSAVAR workshop

This workshop will be multi-stakeholder, multi-disciplinary workshop to define irAOPs specific case study for CAR-T cells and CD3-targeted bispecific antibodies. Within this workshop the gaps for where models need to be refined or new models developed.

2nd iteration in vivo and in vitro models IL-2 Moa

This will be the second iteration of the refined in vivo and in vitro models.

1st iteration in vitro & MPS models

This will be a set of models that have been initially refined based upon the outcome of the imSAVAR workshops on the different in vitro MPSs models developed to address the gaps in the irAOPs This will be a report that defines the refinements and describes and confirmatory work that has been done

2nd iteration to characterize molecular mechanism leading to irAEs

2nd iteration of the characterizing molecular mechanisms of irAEs.

1st iteration to characterize molecular mechanism leading to irAEs

A data catalogue of analysed and interpreted high throughput molecular profiling datasets to reveal molecular mechanism leading to irAEs. The exact modelling methods will be based upon the type of profiling data generated in Task 4.2. and the criteria established in the analysis plans.

Catalogue of datasets

This will be a catalogue of the description of different datasets within imSAVAR and external to imSAVAR that are relevant. This will support the cataloguing of datasets in relation to the immune safety roadmaps from WP 1.

Distributed network biobanking system

A system the process of know which types of samples are available where and support the process of accessing them.

Network of disease domain providers for providing samples

A defined network of centres and defined processes for accessing samples taking into consideration ethics and data privacy concerns. The report on this deliverable will include a description of how this network was used in during the implementation of imSAVAR

1st iteration of advanced immune cell profiling

A dataset of high throughput molecular profiling datasets. The exact molecular profiling techniques will be based upon the outcomes of the workshops, the progress in model, development, and the criteria established in the analysis plans. This will have undergone initial bioinformatic processings to produce a dataset that is useful for identifying biomarkers as well as mechanistic insights from the models being refined and developed in imSAVAR.

2nd iteration of advanced immune cell profiling

2nd iteration of the molecular profiling datasets.

Publications

The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate

Author(s): Sorwe Mojtahed Poor, Marina Henke, Thomas Ulshöfer, Michaela Köhm, Frank Behrens, Harald Burkhardt, Susanne Schiffmann
Published in: Rheumatology, Issue 62, 2023, Page(s) 3993-3999, ISSN 1462-0324
Publisher: Oxford University Press
DOI: 10.1093/rheumatology/kead177

A time-resolved meta-analysis of consensus gene expression profiles during human T-cell activation

Author(s): Michael Rade; Sebastian Böhlen; Vanessa Neuhaus; Dennis Löffler; Conny Blumert; Maximilian Merz; Ulrike Köhl; Susann Dehmel; Katherina Sewald; Kristin Reiche
Published in: Genome Biology, 2023, ISSN 1474-760X
Publisher: Springer Nature
DOI: 10.1186/s13059-023-03120-7

CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma

Author(s): Sabrina Prommersberger, Michael Reiser, Julia Beckmann, Sophia Danhof, Maximilian Amberger, Patricia Quade-Lyssy, Hermann Einsele, Michael Hudecek, Halvard Bonig, Zoltán Ivics
Published in: Gene Therapy, Issue 28, 2021, Page(s) 560-571, ISSN 0969-7128
Publisher: Nature Publishing Group
DOI: 10.1038/s41434-021-00254-w

Immunocompetent cancer-on-chip models to assess immuno-oncology therapy

Author(s): Maulana, Tengku Ibrahim; Kromidas, Elena; Wallstabe, Lars; Cipriano, Madalena; Alb, Miriam; Zaupa, Cécile; Hudecek, Michael; Fogal, Birgit; Loskill, Peter
Published in: Advanced Drug Delivery Reviews, 2021, Page(s) 281-305, ISSN 0169-409X
Publisher: Elsevier BV
DOI: 10.1016/j.addr.2021.03.015

Patient-derived tumoroids and proteomic signatures: tools for early drug discovery

Author(s): Hélène Lê, Jules Deforges, Pasquale Cutolo, Anissa Lamarque, Guoqiang Hua, Véronique Lindner, Shreyansh Jain, Jean-Marc Balloul, Nadia Benkirane-Jessel, Eric Quéméneur
Published in: Frontiers in Immunology, Issue 15, 2024, ISSN 1664-3224
Publisher: frontiers
DOI: 10.3389/fimmu.2024.1379613

A Spatial Transcriptomics Browser for Discovering Gene Expression Landscapes across Microscopic Tissue Sections

Author(s): Maria Schmidt; Susanna Avagyan; Kristin Reiche; Hans Binder; Henry Loeffler-Wirth
Published in: Current Issues in Molecular Biology, 2024, ISSN 1467-3037
Publisher: Caister Academic Press
DOI: 10.3390/cimb46050284

Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells

Author(s): Tengku Ibrahim Maulana; Claudia Teufel; Julia Roosz; Lisa Lazarevski; Francijna E. van den Hil; Lukas Scheller; Valeria Orlova; André Koch; Michael Hudecek; Miriam Alb; Peter Loskill
Published in: Cell Stem Cell, Issue Cell Press, 2024, ISSN 1934-5909
Publisher: Cell Press
DOI: 10.1016/j.stem.2024.04.018

Immuno-inflammatory in vitro hepatotoxicity models to assess side effects of biologicals exemplified by aldesleukin

Author(s): Luise A. Roser; Sonja Luckhardt; Nicole Ziegler; Dominique Thomas; Pia Viktoria Wagner; Georg Damm; Andrea Scheffschick; Philip Hewitt; Michael J. Parnham;Susanne Schiffmann
Published in: Frontiers in Immunology, 2023, ISSN 1664-3224
Publisher: Frontiers Media SA
DOI: 10.3389/fimmu.2023.1275368

Tutorial on survival modeling with applications to omics data

Author(s): Zhi Zhao, John Zobolas, Manuela Zucknick, Tero Aittokallio
Published in: Bioinformatics, Issue 40, 2024, ISSN 1367-4811
Publisher: Oxford University Press
DOI: 10.1093/bioinformatics/btae132

Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer

Author(s): Christina Plattner, Giorgia Lamberti, Peter Blattmann, Alexander Kirchmair, Dietmar Rieder, Zuzana Loncova, Gregor Sturm, Stefan Scheidl, Marieke Ijsselsteijn, Georgios Fotakis, Asma Noureen, Rebecca Lisandrelli, Nina Böck, Niloofar Nemati, Anne Krogsdam, Sophia Daum, Francesca Finotello, Antonios Somarakis, Alexander Schäfer, Doris Wilflingseder, Miguel Gonzalez Acera, Dietmar Öfner, Lukas A.
Published in: iScience, Issue 26, 2024, Page(s) 108399, ISSN 2589-0042
Publisher: Elsevier, Cell Press (iScience)
DOI: 10.1016/j.isci.2023.108399

Transcriptional states of CAR-T infusion relate to neurotoxicity – lessons from high-resolution single-cell SOM expression portraying

Author(s): Henry Loeffler-Wirth, Michael Rade, Arsen Arakelyan, Markus Kreuz, Markus Loeffler, Ulrike Koehl, Kristin Reiche, and Hans Binder
Published in: Frontiers in Immunology, 2022, ISSN 1664-3224
Publisher: Frontiers Media SA
DOI: 10.3389/fimmu.2022.994885

In vitro vascularized immunocompetent patient-derived model to test cancer therapies

Author(s): Hélène Lê, Jules Deforges, Guoqiang Hua, Ysia Idoux-Gillet, Charlotte Ponté, Véronique Lindner, Anne Olland, Pierre-Emanuel Falcoz, Cécile Zaupa, Shreyansh Jain, Eric Quéméneur, Nadia Benkirane-Jessel, Jean-Marc Balloul
Published in: iScience, Issue 26, 2024, Page(s) 108094, ISSN 2589-0042
Publisher: Elsevier, Cell Press (iScience)
DOI: 10.1016/j.isci.2023.108094

Tumor-specific T cells support chemokine-driven spatial organization of intratumoral immune microaggregates needed for long survival

Author(s): Ziena Abdulrahman; Saskia J Santegoets; Gregor Sturm; Pornpimol Charoentong; Marieke E Ijsselsteijn; Antonios Somarakis; Thomas Höllt; Francesca Finotello; Zlatko Trajanoski; Sylvia L van Egmond; Dana A M Mustafa; Marij J P Welters; Noel F C C de Miranda; Sjoerd H van der Burg
Published in: Journal for ImmunoTherapy of Cancer, 2022, ISSN 2051-1426
Publisher: Society for Immunotherapy of Cancer
DOI: 10.1136/jitc-2021-004346

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies.

Author(s): Xiang Zhou; Leo Rasche; K. Martin Kortüm; Sophia Danhof; Michael Hudecek; Hermann Einsele
Published in: Frontiers in Immunology, 2020, ISSN 1664-3224
Publisher: Frontiers Media SA,Frontiers Media S.A.
DOI: 10.3389/fimmu.2020.620312

The Leipzig Health Atlas - An open platform to present, archive and share bio-medical data, analyses and models online

Author(s): Toralf Kirsten, Frank A. Meineke, Henry Loeffler-Wirth, Christoph Beger, Alexandr Uciteli, Sebastian Stäubert, Matthias Löbe, René Hänsel, Franziska G. Rauscher, Judith Schuster, Thomas Peschel, Heinrich Herre, Jonas Wagner, Silke Zachariae, Christoph Engel, Markus Scholz, Erhard Rahm, Hans Binder, Markus Loeffler
Published in: Methods of Information in Medicine, 2022, ISSN 0026-1270
Publisher: Schattauer
DOI: 10.1055/a-1914-1985

Necessity for next-generation quality assessment of CAR T cell manufacturing and advancedtherapy guidance

Author(s): Barbara Seliger, Kristin Reiche, Chiara Massa, Stephan Fricke, Gerno Schmiedeknecht, Friedemann Horn, Conny Blumert, Miriam Alb, Michael Hudecek, Ulrike Koehl
Published in: Cell & Gene Therapy Insights, 2020, ISSN 2059-7800
Publisher: BioInsights Publishing
DOI: 10.18609/ioi.2020.019

EnrichIntersect: an R package for custom set enrichment analysis and interactive visualization of intersecting sets

Author(s): Zhi Zhao, Manuela Zucknick, Tero Aittokallio
Published in: Bioinformatics Advances, 2022, ISSN 2635-0041
Publisher: Oxford University Press
DOI: 10.1093/bioadv/vbac073

Interleukin-2-induced skin inflammation

Author(s): Charline Sommer; Jarish Cohen; Susann Dehmel; Vanessa Neuhaus; Dirk Schaudien, Armin Braun; Katherina Sewald; Michael Rosenblum
Published in: European Journal of Immunology, 2024, ISSN 1521-4141
Publisher: Wiley-VCH GmbH
DOI: 10.1002/eji.202350580

Vascularized patient-derived tumoroids supplemented with immune cells to predict response towards treatment for lung cancer patients

Author(s): Hélène Lê; Charlotte Ponté; Jules Desforges; Guoqiang Hua; Ysia Idoux-Gillet; Véronique Lindner; Anne Olland; Pierre-Emanuel Falcoz; Cécile Zaupa; Eric Quéméneur; Jean-Marc Balloul; Nadia Jessel
Published in: iScience, 2023, ISSN 2589-0042
Publisher: Elsevier
DOI: 10.21203/rs.3.rs-2560741/v1

Bridging therapy-induced phenotypes and genetic immune dysregulation to study interleukin-2-induced immunotoxicology

Author(s): Charline Sommer, Sophie Jacob, Tonia Bargmann, Muhammad Shoaib, Basel Alshaikhdeeb, Venkata P. Satagopam, Susann Dehmel, Vanessa Neuhaus, Armin Braun, Katherina Sewald
Published in: Clinical Immunology, 2024, ISSN 1573-2592
Publisher: Springer Nature
DOI: 10.1016/j.clim.2024.110288

Tissue-specific identification of multi-omics features for pan-cancer drug response prediction

Author(s): Zhi Zhao, Shixiong Wang, Manuela Zucknick, Tero Aittokallio
Published in: iScience, Issue 25, 2024, Page(s) 104767, ISSN 2589-0042
Publisher: Elsevier
DOI: 10.1016/j.isci.2022.104767

Multiplexed Organ-on-Chips with integrated macro valves for automated cell culture

Author(s): Bossink, Elsbeth G.B.M.; Vollertsen, Anke Ricarda; Hagen, Lieke P.; van der Meer, A.; Segerink, Loes; Odijk, Mathieu
Published in: Issue 4, 2021
Publisher: µTAS 2021

Automated medium recirculation using macro valves for high flow rates in an endothelial cell culture chip

Author(s): Bossink, Elsbeth G.B.M.; Vollertsen, Anke Ricarda; Segerink, Loes; van der Meer, A.; Odijk, Mathieu
Published in: Issue 13, 2021
Publisher: µTAS 2021

Teclistamab impairs detection of BCMA CAR-T cells

Author(s): Bettina Glatte; Kerstin Wenk; Anja Grahnert; Maik Friedrich; Maximilian Merz; Vladan Vucinic; Luise Fischer; Kristin Reiche; Miriam Alb; Michael Hudecek; Paul Franz; Stephan Fricke; Uwe Platzbecker; Ulrike Koehl; Ulrich Sack; Andreas Boldt; Sunna Hauschildt; Ronald Weiss
Published in: Blood Advances, 2023, ISSN 2473-9529
Publisher: American Society of Hematology
DOI: 10.1182/bloodadvances.2023009714

Solid tumor-on-chip model for efficacy and safety assessment of CAR-T cell therapy

Author(s): Tengku Ibrahim Maulana, Claudia Teufel, Madalena Cipriano, Lisa Lazarevski, Francijna E. van den Hil, Valeria Orlova, André Koch, Miriam Alb, Michael Hudecek, Peter Loskill
Published in: 2023
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.07.13.548856

Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways

Author(s): Alexander Mazein, Muhammad Shoaib, Miriam Alb, Christina Sakellariou, Charline Sommer, Katherina Sewald, Kristin Reiche, Patricia Gogesch, Luise A Roser, Samira Ortega Iannazzo, Sapna Sheth, Susanne Schiffmann, Zoe Waibler, Vanessa Neuhaus, Susann Dehmel, Venkata Satagopam, Reinhard Schneider, Marek Ostaszewski, Wei Gu
Published in: 2023
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.03.21.533620

Deliverables

Publications

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