SMART-ToC Tumor-on-Chip (ToC) platform incorporating Sensing hydrogel MAtrices

SMART-ToC is conducted by a transdisciplinary team set to develop an advanced breast tumor-on-chip model as a tool to test novel anti-cancer therapies and enable personalized medicine.

4 years | 4 countries | 6 societal & industry partners & 4 research institutions (2 technical universities, 1 applied science university & 1 university medical centre)

Tumor tissues are highly heterogeneous and vary with disease progression. Heterogeneity, as reported for certain microenvironmental parameters (oxygen, pH, tissue stiffness), often correlates with poor treatment success. Yet, current in-vitro/in-vivo tumor models do not properly incorporate spatiotemporal variations and thus have limited translational value. Therefore, innovative approaches are needed for advanced modeling of the tumor microenvironment, that correlate spatiotemporal alterations to therapy responses, to ultimately understand interrelationships and facilitate cost-effective (immuno)therapy development. Such approaches will be a gamechanger towards in vitro pharmacokinetics studies and provide a trajectory towards personalized medicine, after model personalization using patient-derived materials.

SMART-ToC will develop an advanced breast tumor-on-chip model incorporating essential cellular, physical, and chemical elements that impact therapeutic response; validate this model for antibody-drug conjugates and immunotherapies; and conduct an innovation trajectory towards societal acceptance. The proposed breast tumor-on-chip comprises a 3D-multicellular culture of breast tumor, innate immune cells, cancer- associated fibroblasts, and a vasculature, in a tunable (animal-free) hydrogel matrix equipped with sensors to map in 3D important microenvironmental parameters (pH, oxygen and stiffness). The model will be applied to evaluate therapeutic efficacy for antibody- and virus-based immunotherapies, in comparison to healthy breast tissue for tolerability studies.

Working packages (WP)

WP1| SMART hydrogels with tunable properties and sensing capabilities.

WP2| SMART-ToC (tumor-on-chip) model.

WP3 | Model validation for therapeutic applications

WP4 | Societal and ethical parallel trajectory.

About the partners

Scientific partners

UTwente | Le Gac’s lab: Applied Microfluidics for Bioengineering Research (AMBER)

Prof. Le Gac is chairing the Applied Microfluidics for Bioengineering Research group at the UT and has over 20 years’ experience in microfluidics and organ-on-chip technologies. She develops, with her team, innovative miniaturized devices for cancer research and reproductive medicine, and to evaluate the impact of plastics on human health. She has ample experience with industrial collaborations (e.g., OTP-NWO, TKI-LSH Health-Holland, Merck Serono, Hitachi), and technology transfer. She is the consortium coordinator and the main responsible for WP2. Within SMART-ToC, her team will develop the microfluidic platform, optimize cell patterning to create a vascularized tumor model, and conduct first-stage drug testing using chemotherapeutics.

UTwente | Paez lab

Dr. Paez is Associate Professor at the Developmental Bioengineering Group of the BioEngineering Technologies department at the UT and has expertise in synthetic macromolecular and biomaterials chemistry as well as soft matter applied to biomedicine. She started her independent career in 2019 as a Project Leader at INM—Leibniz Institute for New Materials in Germany and then joined the UT in 2021 as a tenure tracker. She has experience in collaborative projects with industry and in transfer of technology. She is the consortium co-coordinator and the main responsible for WP1. Within SMART-ToC, her team will develop the sensing hydrogel matrix with modulable properties to embed the tumor cells.

Industrial partners

Societal partners

Outreach

Do you want to know more about the importance of tumor microenvironment and tumor on chip technologies? Check this interactive website: https://toc-tme-amber.netlify.app/.

Funding

This project with file number KICH1.ST04.22.015 of the research programme KIC - MISSION Emerging Key Enabling Technologies is financed by the Dutch Research Council (NWO).