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 HOPE; 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
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
