Immune Cell Characterization Using Novel Marker Signatures
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Solution Overview
Problem
Current methods for characterizing and identifying immune cells, particularly dendritic cells, are limited by biased marker expression, leading to inaccurate assignment of function and ontogeny, and there is a need for novel markers and targets to modulate immune responses effectively.
Innovation Solution
Discovery of novel immune cells and markers, including specific gene signatures, that characterize and differentiate immune cells, such as those expressing HLA-DR and lacking CD3, CD56, CD19, and CD14, and the development of kits and methods for detecting and isolating these cells, enabling more precise characterization and modulation of immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If traditional surface markers are used to define leukocyte populations, then classification is simplified, but accuracy and completeness of immune cell identification deteriorates due to inherent bias
Solution Approach 1:
The patent segments the immune cell classification system by dividing it into multiple independent marker panels, each targeting specific cell types. Instead of relying on a single biased marker set, the invention creates separate classification pathways for different leukocyte populations (T cells, B cells, NK cells, dendritic cells, monocytes) using distinct marker combinations, thereby reducing cross-contamination of classification criteria and improving overall accuracy
Solution Approach 2:
The patent transitions from traditional two-dimensional flow cytometry analysis to high-dimensional mass cytometry (CyTOF) that can simultaneously measure 30-40 different protein markers. This dimensional expansion allows simultaneous visualization of multiple marker expressions without the compensation issues inherent in fluorescent-based systems, enabling more precise cell identification and discovery of rare cell populations
2Ease of manufacture
If a restricted set of surface markers is used, then the classification method is easier to implement, but the functional assignment and ontogeny characterization of immune cells becomes inaccurate
Solution Approach 1:
The patent develops a universal marker panel set that can simultaneously identify and characterize multiple immune cell types within a single assay. The standardized panel includes markers for T cells (CD3, CD4, CD8), B cells (CD19, CD20), NK cells (CD56, CD16), dendritic cells (CD11c, CD123, CLEC9A), and monocytes (CD14, CD16), allowing one methodology to serve multiple diagnostic and research purposes while maintaining high reliability across different cell types
Solution Approach 2:
The patent changes the detection parameters by transitioning from fluorescent markers to metal-isotope-based markers detectable by mass cytometry. This parameter change enables simultaneous detection of numerous markers without spectral overlap, providing more reliable functional assignment and ontogeny characterization through precise measurement of marker expression levels and patterns
3Ease of operation
If conventional dendritic cell markers (CD11c, CD123) are used, then cell isolation is simplified, but the discovery of novel DC subtypes and accurate characterization is limited
Solution Approach 1:
The patent segments the dendritic cell population into distinct subtypes by introducing additional marker dimensions beyond traditional CD11c and CD123. It divides DCs into conventional DCs (cDCs) further classified as CD141+ or CD1C+, and plasmacytoid DCs (pDCs) as CD123+, with each subtype having unique functional characteristics. This segmentation allows precise isolation and study of each DC subtype without cross-contamination
Solution Approach 2:
The patent adds new marker dimensions (CLEC9A, FCGR2B, FCGR3A, CD45RA, CD100, CD34) to the traditional DC marker set, creating a multi-dimensional classification space. This dimensional expansion reveals previously undetectable DC subtypes and their transitional states, enabling comprehensive characterization of DC heterogeneity and ontogeny while maintaining practical isolation capabilities
Data Source
AI summary
The present invention provides isolated immune cells, immune cell populations and compositions, as well as markers, marker signatures and molecular targets characterising the immune cells. The cell products, substances, compositions, markers, marker signatures, molecular targets, kits of parts and methods of the present invention provide for new ways to characterise, evaluate and modulate the immune system and immune responses.