TissUse and Roche have signed a cooperating agreement to develop human-relevant in vitro assays based on TissUse’s Multi-Organ-Chip technology.
Under the terms of the collaboration agreement, TissUse will provide its Multi-Organ-Chip (MOC) technology as a highly versatile tool to develop in vitro assays to increase prediction of safety liabilities of drug candidates early on. During the three-year project phase, TissUse and Roche are combining their broad knowledge and expertise to establish assays for the assessment of lineage-specific hematopoietic toxicity and the evaluation of pharmacokinetics of therapeutic antibodies.
MOC-based assay for long-term repeated dose testing of lineage-specific haematotoxicity
In vitro assessment of potential haematopoietic toxicity of drug candidates is an important aspect in drug research and development. The project aims to establish an assay for long-term repeated dose testing of drug candidates in a dynamic bone marrow model to mimic in vivo dosing scenarios and aid modelling approaches. A second development phase will focus on combining the bone marrow model with a liver model in order to assess metabolic activation of candidates.
MOC-based antibody PK assay
Mechanisms contributing to the pharmacokinetics of intravenously administered pharmaceutical antibodies in the human body are not yet fully understood. The partners therefore aim to establish an assay for the in vitro assessment of key pharmacokinetic mechanisms of therapeutic antibodies. Major emphasis will be given to modelling the role of different cell types in modulating antibody clearance and intracellular trafficking.
“We are excited to form this long-term partnership which will address fundamental aspects of antibody kinetics and organ-specific NCE toxicity by applying our Multi-Organ-Chip technology,” says Dr. Uwe Marx, CEO of TissUse. “Combining several organ models in a circulatory system is the next necessary step to assess systemic toxicity and establish complex in vitro disease models in order to bring innovative medicine faster to the patient.”
About the Multi-Organ-Chip (MOC) technology
TissUse proprietary commercial MOC technology platform is a microfluidic microphysiological systems platform capable of maintaining and culturing miniaturized organ equivalents emulating the biological function of their respective full-size counterparts over long periods. Major features of living biology such as pulsatile fluid flow, mechanical and electrical coupling, physiological tissue-to-fluid and tissue-to-tissue ratios are incorporated. This supports the development of a large variety of substance test assays ranging from acute and repeated dose toxicity to long-term disease treatment (efficacy). The technology allows for flexible and customized combination of different tissue constructs or organ equivalents on a disposable chip-based microphysiological system. The number of organ equivalents supported by the platform ranges from single organ culture up to an organ number supporting the study of complex organ interactions. First commercially available platforms support single-, two-, three and four-organ culture. Examples of organ models available at TissUse include: liver, intestine, skin, vasculature, neuronal tissue, cardiac tissue, cartilage, pancreas, kidney, hair follicle, lung tissue, fatty tissue, tumor models and bone marrow. Further organ models are being developed. The platform further comprises Control Units operating up to four MOCs simultaneously. These Control Units provide the flexibility needed to control and monitor any on-chip organ arrangement. Some of the existing models include different levels of immunocompetence such as immune cells in skin biopsies, Langerhans cells in full-thickness skin equivalents, hematopoietic progenitor cells in the bone marrow model and Kupffer cells in liver spheroids.
Under the terms of the collaboration agreement, TissUse will provide its Multi-Organ-Chip (MOC) technology as a highly versatile tool to develop in vitro assays to increase prediction of safety liabilities of drug candidates early on. During the three-year project phase, TissUse and Roche are combining their broad knowledge and expertise to establish assays for the assessment of lineage-specific hematopoietic toxicity and the evaluation of pharmacokinetics of therapeutic antibodies.
MOC-based assay for long-term repeated dose testing of lineage-specific haematotoxicity
In vitro assessment of potential haematopoietic toxicity of drug candidates is an important aspect in drug research and development. The project aims to establish an assay for long-term repeated dose testing of drug candidates in a dynamic bone marrow model to mimic in vivo dosing scenarios and aid modelling approaches. A second development phase will focus on combining the bone marrow model with a liver model in order to assess metabolic activation of candidates.
MOC-based antibody PK assay
Mechanisms contributing to the pharmacokinetics of intravenously administered pharmaceutical antibodies in the human body are not yet fully understood. The partners therefore aim to establish an assay for the in vitro assessment of key pharmacokinetic mechanisms of therapeutic antibodies. Major emphasis will be given to modelling the role of different cell types in modulating antibody clearance and intracellular trafficking.
“We are excited to form this long-term partnership which will address fundamental aspects of antibody kinetics and organ-specific NCE toxicity by applying our Multi-Organ-Chip technology,” says Dr. Uwe Marx, CEO of TissUse. “Combining several organ models in a circulatory system is the next necessary step to assess systemic toxicity and establish complex in vitro disease models in order to bring innovative medicine faster to the patient.”
About the Multi-Organ-Chip (MOC) technology
TissUse proprietary commercial MOC technology platform is a microfluidic microphysiological systems platform capable of maintaining and culturing miniaturized organ equivalents emulating the biological function of their respective full-size counterparts over long periods. Major features of living biology such as pulsatile fluid flow, mechanical and electrical coupling, physiological tissue-to-fluid and tissue-to-tissue ratios are incorporated. This supports the development of a large variety of substance test assays ranging from acute and repeated dose toxicity to long-term disease treatment (efficacy). The technology allows for flexible and customized combination of different tissue constructs or organ equivalents on a disposable chip-based microphysiological system. The number of organ equivalents supported by the platform ranges from single organ culture up to an organ number supporting the study of complex organ interactions. First commercially available platforms support single-, two-, three and four-organ culture. Examples of organ models available at TissUse include: liver, intestine, skin, vasculature, neuronal tissue, cardiac tissue, cartilage, pancreas, kidney, hair follicle, lung tissue, fatty tissue, tumor models and bone marrow. Further organ models are being developed. The platform further comprises Control Units operating up to four MOCs simultaneously. These Control Units provide the flexibility needed to control and monitor any on-chip organ arrangement. Some of the existing models include different levels of immunocompetence such as immune cells in skin biopsies, Langerhans cells in full-thickness skin equivalents, hematopoietic progenitor cells in the bone marrow model and Kupffer cells in liver spheroids.
