Advanced Cell Models for Drug Discovery and Translational Research
Leveraging ATMP development with advanced human cell models reconstructing disease microenvironments
Advanced Cell Models at iBET
In the last 15+ years, iBET has built solid competences developing and implementing 3D in vitro human models to tackle preclinical challenges in the imminent areas of cancer immunotherapies and gene therapies.
Our advanced cell models reproduce key features of cellular microenvironments and their deregulation in disease, representing valuable platforms to accelerate drug discovery and development in the pharma industry.
In this R&D area we focus on:
- Platform Development
- Innate immune microenvironments in therapeutic response
- Preclinical & Translational Research
Platform Development
We develop immunocompetent 3D in vitro models to study the impact of the cell microenvironment on therapeutic responses in tissues such as the central nervous system, liver, and solid tumors. Depending on the target tissue and available cell sources, the culture systems employed may include 3D co-cultures, primary cultures of patient-derived cells and differentiation of human induced-pluripotent stem cells (hiPSCs). A strong focus is on a comprehensive functional characterization of the models, assuring reproducible and scalable bioprocesses.
Innate immune microenvironments in therapeutic response
We interrogate innate immunity mechanisms modulating the cell microenvironment in disease to better understand therapeutic responses (ex. to rAAV vectors and monoclonal antibodies). We focus on inflammation and immunosuppression as key biological events underlying the crosstalk between tissue-/tumor-resident macrophages and other resident cells.
We explore cell-extracellular matrix (ECM) crosstalk and protein-protein and protein-glycan interactions to address the pathological consequences of microenvironment remodeling in the context of cancer, neurodegeneration, aging and infection.
Allow the study of innate immune responses to gene therapy vectors (rAAV) by addressing the cellular crosstalk between tissue-resident cells, including immune cells.
Targets:
- neuron-astrocyte-microglia (CNS)
- hepatocyte-Kupffer cell-liver sinusoidal endothelial cell (liver)
Reproduce the build-up of immunosuppressive microenvironments allowing for in-depth evaluation of therapeutic responses to advanced therapies.
Targets:
- astrocyte-microglia/macrophage crosstalk in pediatric gliomas
- tumor glycan-macrophage lectin interactions shaping immunosuppressive macrophages
Preclinical & Translational Research
We evaluate the contribution of the innate immune microenvironment to therapeutic response/resistance, in collaboration with biopharma industry partners and clinicians. Ongoing applications include target identification and validation, pre-clinical assays, prediction of patient outcomes and predictive biomarker discovery.
Disease Targets & Research Topics
Our 3D human cell model portfolio covers the areas of the central nervous system, liver, and solid tumors.
Related Technologies
Cell Sources and Culture Approaches
Cell Sources and Culture Approaches
We have wide cell culture expertise to develop our in vitro platforms. We mostly work with 3D co-culture systems and use a variety of cell sources such as human induced-pluripotent stem cells (hiPSC) and other patient-derived cells, as tissue explants or primary cultures. We generate human stem-cell derived CNS and liver models as well as immune cell types of interest through multi-step differentiation protocols.
Bioreactor Platforms
Bioreactor Platforms
We employ iBET’s expertise in bioreactor technology to reproduce physiologically relevant cell interactions and environmental conditions in our 3D models. This technology allows for tight control of culture parameters (pO2, pH and perfusion rate), high-throughput, and easy maintenance of long-term cultures. Available systems include: glass (80 mL to 5 L) and disposable systems (15 ml to 50 L).
Molecular and Cell Biology Tools
Molecular and Cell Biology Tools
For model characterisation and functional studies, we employ techniques including CRISPR/Cas9 technology, gene expression analysis, multicolor flow cytometry, protein separation and detection methods, including multiplexing.
Imaging
Imaging
To assess cell morphology, functionality, and marker expression we employ state-of-the art imaging techniques. Confocal microscopy (2-photon, spinning disk, light sheet) is used for live fluorescence-based assays and immunofluorescence characterization. Scanning and transmission electron microscopy are used for morphological analysis.
Metabolic Characterization
Metabolic Characterization
We employ a wide range of equipment to assess metabolic function: CEDEX Bio for detection of metabolites, HPLC, NMR, LC-MS and GC-MS analytical techniques, integrated through metabolic flux analysis methodologies.
Multi-Omics Tools
Multi-Omics Tools
For a comprehensive assessment of cell-cell, cell-ECM interactions and therapeutic responses elicited by ATMPs in our 3D cell models, we use multi-omics tools, such as transcriptomics (bulk and single-cell RNA-Seq), proteomics, metabolomics and fluxomics. Know more in our Mass Spectrometry Support Unit page.
Highlights
Related Teams
Advanced Cell Models Lab
Catarina Brito
Lab Head, Advanced Cell Models Laboratory
Leveraging ATMP development with advanced human cell models
Translational Immunology Lab
Nádia Duarte
Senior Scientist, Translational Immunology Lab
Strengthening immunology expertise at iBET, with a focus on developing tools and strategies to test and potentiate the effectiveness of advanced cell immunotherapies
Cellular Bioprocesses Lab
Paula Alves
Chief Executive Officer (CEO) | Head of Cell Bioprocesses Lab
Improving cellular bioprocess understanding using state-of-the-art bioanalytics and omics tools.