Novel Research Tools for Immuno-oncology Drug Discovery
Built on 20+ years’ experience on development of novel assays and ex vivo tissue culture methods for drug screening, Misvik is developing three different assay platforms to serve the needs of immuno-oncological drug discovery & development and diagnostic modelling of therapy efficacy at an individual patient level.
- High-throughput 3D co-culture assays using patient derived models
- Self-organizing 3D organoid microarrays
- Proteomic immunophenotyping technology for massively parallel functional immunophenotyping for ex vivo drug screening
3D co-culture drug screening assays with patient derived functional tumor models
Co-culture assays integrate tumor spheroid models with allogenic or HLA matched immune cells for analysis of e.g., drug induced:
-Immune cell migration
-Immune cell homing/aggregation to tumor cells
-Immune cell mediated tumor cell killing
-Rapid + scalable
-Readily compatible with large compound collections
-Compatible with multiplexed immunofluorescence readouts
-Machine learning powered morphometric analyses for in depth biological
Self-organizing 3D organoid microarrays
Conventional spheroid/organoid assays are inherently limited by the difficulty of controlling spehoid formation (size, moprology). Our novel miniaturized 3D organoid array approach combines simplified 3D cell culture with advanced microarray manufacturing techniques into a platform that results in complex, highly controllable self-organizing microtissues that allow reproducible formation of highly uniform organoids from various cells of origin and various combinations of these to create new tools for drug discovery and biomedical research.
-Validated for 3D cell culture compatibility with a panel of 98 commercial cell lines and 45 patient derived tumor models
-Combined with an in-house developed image analysis pipeline that combines conventional quantitative morphometrics and deep learning convolutional neural networks based qualitative classification of phenotypes
-Adaptation to precision medicine and drug sensitivity testing using patient-derived ex vivo cell cultures ongoing
Functional proteomic immunophenotyping
A novel protein microarray technology for treatment induced immune response profiling
-Despite the recent rapid development of novel lineage tracing techniques including mass cytometry, these methods are not feasible for high-throughput drug screening assays due to the high number of cells (and multiple sample preparation steps) needed for analyses.
-The proteomics assay strategy is based on quantitative analysis of marker proteins as a surrogate for lineage tracing. A single cell sample from a 384-well format assay can be analyzed with 10´s to 100´s of different antibodies detecting both total protein and e.g., phosphorylation levels.
-The method is compatible with all therapeutic entities (small molecule, Mab´s etc.).
-Custom assay options for any given therapeutic setting/target cell type/immunophenotypic marker.