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 cytotoxic 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 services

IBR Inc. scientists have vast experience in 3D biomimetic microtissues models for testing cytotoxic compounds and immunotherapy agents. Our services for 3D cell-based assays include:

 

 

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.

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 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 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 obstacles antibody penetration. Targeting of surface antigens on target cells is therefore more demanding compared to 2D monolayers.

IBR Inc. 3D services offer custom specific development of 3D co-culture models using a broad panel of cell lines and primary cells including freshly isolated PBMCs.

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
  • Analysis of supernatants (cytometric bead array for quantitation of cytokines, LDH measurement for quantitation of target cell death)
  • ATP measurement for quantification of cell proliferation
  • Confocal microscopy and immunofluorescence for assessment of antibody penetration and targeting
  • Live microscopy for monitoring microtissue compaction and growth
  • Microscopic assessment of microtissue size
  • Flow cytometry analysis and cell phenotyping

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.

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