Immunology and Immuno-Oncology

Inflammation is a complex process involving many aspects of biology.

Recent advances in the field of immuno-oncology, such as CAR-T, are driving how we harness the immune system to fight disease.

Objective

Therapeutic approaches in macrophage biology can involve polarizing towards a preferred phenotype (M1 vs M2), depending on the application.

This assay was developed to identify M1 vs M2 cell populations

Design

We optimized across several polarization paradigms to skew final populations towards a complete M1 vs M2 endpoint.

Subsequent compound testing identified compounds that could modulate this polarization process.

Advantages

Imaging unambiguously identifies cell populations (M1 vs M2) and allows for quantification of intracellular markers.

Signalling pathways can be examined (phosphorylation, nuclear translocation) as part of mechanism-of-action studies

Immunology and I/O: M1/M2 Activation

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Immunology and I/O: CellHandler PDx Usage

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Objective

Correlate in vivo data on chemotherapy sensitivity with tumor fragments generated from PDX tumors

Design

Orthotopic PDX models with known sensitivity/resistance patterns were fragmented and allocated to microwell plates for compound testing

Advantages

The Yamaha Motors Cell Handler allocates fragments by size, shape, and other features to microwell plates, allowing for reproducible baseline starting materials.

Chemotherapy sensitivity and resistance can be tested in vitro, allowing for more precision in concentration selection, as well as combination therapy evaluation.

Objective

Quantify immune-cell mediated activities (recruitment and killing) on solid tumor models

Design

Co-culture of human PBMCs stimulated to activate various immune subpopulations and human solid tumor cell lines

Advantages

Immune cell clustering around tumor cells may precede tumor cell death, and may also occur independently, providing a rationale for combination studies (increase immune cell clustering plus cell death via checkpoint inhibition).

Molecules/cell therapies that work via different mechanisms of action (T-cells, monocytes, macrophages, NK cells, CAR-T) can be evaluated

Immunology and I/O: T Cell Killing & Clustering

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