Three-dimensional (3D) biomimetic microtissues
3D biomimetic microtissues composed of tumor cells, fibroblasts and immune cells provide additional information on the effects of immunotherapies compared to classical 2D systems.
3D models are a versatile platform, suitable for testing engineered immunoagents like antibodies with enhanced effector function, immunocytokines, T-cell binders and immune checkpoint modulators in monotherapy and in combination as well as cytotoxicity of compounds. They enable long-term co-culture with immune cells and characterization of immune cell subpopulations opening up new ways to assess the enhancement of NK cell, T-cell and NKT cell recruitment and activity (cytokine/chemokine release, infiltration, surface and intracellular marker expression, elimination of target cells and proliferation).
Advantages over 2D systems
Antibody penetration, immune cell infiltration, antibody targeting and subsequent lymphocyte recruitment and elimination of tumor- or fibroblast- microtissue areas represent additional aspects of the activity of cancer immunotherapy agents that cannot be assessed in a 2D system. Additionally, effects of combination therapies can be better evaluated in 3D systems, since such models better support a physiological immunomodulatory function than 2D systems.
Advantages over in-vivo models
There is a considerable temporal advantage over the in-vivo models because 3D models allow a faster kinetic analysis of therapeutic activity due to fast and efficient immune cell activation and target cell lysis.
Our 3D service concept - one-stop shop
IBR Inc. scientists have vast experience in 3D cellular assays for testing immunotherapy agents and cytotoxicity of compounds.
IBR Inc. 3D services are based on a variety of established models, assays and readouts and make use of the most advanced immunoassay platforms and technologies. This enables to provide 3D services as a one-stop shop that covers the most different needs and to face the most challenging issues in drug testing.
Hanging–drop as well as ultra-low attachment microwell platforms
IBR Inc. scientists have hands-on experience in performing 3D cell-based assays using different 3D platforms, including hanging–drop and ultra-low attachment plates. The choice of platform depends on the assay specific requirements and readouts. IBR Inc. scientists provide excelent support and expertise in selecting the most appropriate platform and tailoring the assay to your specific needs.
Bioprinting technology
Bioprinting is the future of regenerative medicine. Bioinks are cell-compatible liquid matrix preparations that allow printing of 3D structures. They pave the road to develop micro tissues and organoid structures with in-vivo like architecture and cell differentiation.
IBR Inc. is in touch with latest innovations in the field and a premier site to develop optimized 3D models for your advanced compound testing.
3D Scaffolds
A variety of solid scaffolds are available on the market which allow three-dimensional cell growth and are easy to use, biomimetic, and compatible with a variety of cells. IBR Inc. scientists explore the properties of several different 3D scaffolds in order to offer cutting–edge solutions to our clients.
A-C: CD45 immunohistochemical staining, 20x magnification
A: microtissues after 24 hours incubation
B: microtissues after 24 hours incubation with PBMCs
C: microtissues after 24 hours incubation with PBMCs and IL-2
D: schematic representation of tumor/fibroblast microtissue morphology and PBMCs infiltration
3D infiltration assays to assess immune cell recruitment and activation
IBR Inc. offers 3D infiltration assays to evaluate effects of cytokines, immunocytokines, antibodies with enhanced effector function, T-cell binders and immune checkpoint modulators in monotherapy and in combination. We can use freshly isolated human PBMCs, or specifc immune cell subtypes isolated by magnetic bead separation and phenotyped by flow cytometric analysis.
3D cell-based assays to assess cytotoxicity
3D microtissues can be used to assess cytotoxicity of compounds. Cytotoxicity can be assessed on different cell types depending on tissue-specific cytotoxicity of the test compound, using several different readouts. IBR Inc. scientists are versed in evaluating and choicing optimal solutions.
3D cell-based assays to assess antibody penetration and targeting
3D microtissues offer more challenging conditions compared to 2D systems to assess antibody penetration and targeting. The complex tissue-like morphology and architecture of microtissues, generated by co-culturing different cell types, represent a threedimentional barrier that prevents antibody penetration. Targeting of surface antigens on target cells is therefore more demanding compared to 2D monolayers.
Custom assay development of 3D co-culture models
IBR Inc. 3D services offer custom development of 3D co-culture models using a broad panel of cell lines, primary cells, iPS and vascular cells, including freshly isolated PBMCs.
Extensive choice of assay readouts
We are experienced in assessing the results of 3D assays though a variety of readouts for a comprehensive assessment of the mechanisms of action of your molecule in monotherapy and in combination. Our readouts include:
- IHC and quantitative image analysis
IBR Inc. scientists are able to extract high-level information and have vast experience in quantitative image analysis for the evaluation of immunohistochemical staining of 3D cell cultures. Quantification of immune cell infiltration, tumor and stromal areas is of essential importance for the evaluation of complex 3D assays, in order to assess the effects of immunotherapeutic agents.
- Multiplex technologies for quantitation of cytokines in the 3D culture supernatants (cytometric bead array or MSD)
- Flow cytometry analysis and cell phenotyping
- Confocal microscopy and immunofluorescence for assessment of antibody penetration and targeting, cell migration
- Live microscopy for monitoring microtissue compaction and growth
- Microscopic assessment of microtissue size
- Quantitation of target cell death (LDH measurement, colorimetric readout)
- Quantification of cell proliferation (ATP measurement, luminescence readout)
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