The immune component is essential for the biologic response of virtually every tissue to specific stresses. Interspecies differences of the immune system, target homology and class-related properties of biologics and immunomodulatory drugs urge the use of human relevant models to support non-clinical investigations of the underlying molecular mechanisms of disease and immune response to therapies. We develop immunocompetent human cell-based Organ-on-Chip models to monitor immune cell activation, time-resolved cytokine secretion and immune cell migration/chemo-attraction towards tissue specific cell types. Therefore, we investigate immune responses to immunomodulating compounds in the context of disease specific immune response mechanisms and/or of immuno-oncological therapies (e.g. CAR-T cells and antibody-based therapies). The organ-on-chip systems incorporate different types of microphysiological human tissues with various numbers of cell types and degrees of complexity integrated in a vasculature-like perfusion. The immune component is introduced by continuous circulation of PBMCs (or subsets) through the vasculature-like perfusion and/or by integrating tissue-resident immune cells into the 3D tissues. These human immunocompetent on-a-chip models offer a platform for profiling of selected drug candidates to inform early safety liabilities and guide the risk mitigation strategy prior the first-in-human studies.
Funding: WellcomeLeap Dynamic Resilience; WellcomeLeap HOPE; IMI2 imSAVAR; IMI2 Inno4vac; NC3Rs CrackIT;
Publications
J. Rogal, J. Roosz, C. Teufel, M. Cipriano, R. Xu, W. Eisler, M. Weiss, K. Schenke-Layland, P. Loskill
Autologous human immunocompetent white adipose tissue-on-chip
Adv. Sci., 2022, 2104451, https://doi.org/10.1002/advs.202104451
M. Cipriano, K. Schlünder, C. Probst, K. Linke, M. Weiss, M.J. Fischer, L. Mesch, K. Achberger, S. Liebau, M. Mesquida, V. Nicolini, A. Schneider, A.M. Giusti, S. Kustermann, P. Loskill
Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs
Commun. Biol., 2022, 5, 52, https://doi.org/10.1038/s42003-021-02977-3
E. Kromidas, A. Geier, A. Weghofer, H.-Y. Liu, M. Weiss, P. Loskill
Immunocompetent PDMS-free Organ-on-Chip Model of Cervical Cancer Integrating Patient-Specific Cervical Fibroblasts and Neutrophils
Adv. Healthc. Mater., 2023, 2302714, https://doi.org/10.1002/adhm.202302714
Miriam Alb, Kristin Reiche, Michael Rade, Katherina Sewald, Peter Loskill, Madalena Cipriano, Tengku Ibrahim Maulana, Andries D. van der Meer, Huub J. Weener, Laure-Alix Clerbaux, Birgit Fogal, Nirav Patel, Karissa Adkins, Emma Lund, Ethan Perkins, Christopher Cooper, Jan van den Brulle, Hannah Morgan, Tina Rubic-Schneider, Hui Ling, Keith DiPetrillo, Jonathan Moggs, Ulrike Köhl, Michael Hudecek
Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept
J. Immunotoxicol., 2024, 21, S13–S28, https://doi.org/10.1080/1547691X.2024.2345158
Max Urbanczyk, Athar Abuhelou, Marie Köninger, Abiramy Jeyagaran, Daniel Carvajal-Berrio, Ellie Kim, Julia Marzi, Peter Loskill, Shannon L. Layland, Katja Schenke-Layland
Heterogeneity of Endothelial Cells Impacts the Functionality of Human Pancreatic In Vitro Models
Tissue Eng. Part A, 2024, https://doi.org/10.1089/ten.tea.2024.0176
T.I. Maulana, N.R. Wevers, T. Kristoforus, M. Chandler, H. L Lanz, J. Joore, P. Vulto, R. Villenave, S. Kustermann, P. Loskill, K. M Bircsak
Opportunities for microphysiological systems in toxicity testing of new drug modalities
Annu. Rev. Pharmacol. Toxicol., 2025, 65, https://doi.org/10.1146/annurev-pharmtox-061724-080621
T.I. Maulana, C. Teufel, M. Cipriano, J. Roosz, L. Lazarevski, F.E. van den Hil, L. Scheller, V. Orlova, A. Koch, M. Hudecek, M. Alb, P. Loskill
Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells
Cell Stem Cell, 2024, 31, 989-1002, https://doi.org/10.1016/j.stem.2024.04.018
I.T. Maulana, E. Kromidas, L. Wallstabe, M. Cipriano, M. Alb, C. Zaupa, M. Hudescek, B. Fogal, P. Loskill
Immunocompetent cancer-on-chip models to assess immuno-oncology therapy
Adv. Drug. Deliv. Rev., 2021, 173, 281-305, https://doi.org/10.1016/j.addr.2021.03.015
F. Hornung, J. Rogal, P. Loskill, B. Löffler, S. Deinhardt-Emmer
The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections
Int. J. Mol. Sci., 2021, 22, 3456, https://doi.org/10.3390/ijms22073456
