Probe-Based Spatial Genetic Mapping for Tumor Clone Targeting
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Solution Overview
Problem
Current cancer immunotherapies face challenges in effectively targeting clonal populations within tumors due to heterogeneous expression of tumor antigens and MHC proteins, leading to limited efficacy as they often assume uniform expression across the tumor volume.
Innovation Solution
A method for spatially mapping the expression of HLA variants and tumor antigens within a biological sample using probes that hybridize to specific nucleic acid sequences, allowing for the identification and localization of clonal populations, which informs the selection of targeted cancer therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cancer immunotherapies target clonal populations throughout the tumor volume, then treatment coverage is improved, but treatment efficacy deteriorates due to heterogeneous expression of antigens and MHC proteins
Solution Approach 1:
The patent applies local quality by transitioning from uniform treatment assumptions to spatially-resolved analysis. It maps the expression of tumor antigens and MHC proteins at specific locations within the tumor, identifying which clonal populations express these molecules in particular regions. This enables treatment strategies that are tailored to specific spatial zones rather than applying uniformly across the entire tumor volume, thereby improving efficacy by targeting only the most relevant clonal populations.
2Ease of operation
If uniform expression of antigens and MHC proteins is assumed across the tumor, then treatment selection is simplified, but measurement precision deteriorates due to heterogeneous expression patterns
Solution Approach 1:
The patent segments the tumor into distinct spatial regions and identifies separate clonal populations within those regions. By dividing the tumor volume into manageable spatial units and analyzing antigen and MHC protein expression within each segment, the method achieves precise measurement of expression patterns without overwhelming complexity. This segmentation approach maintains ease of operation by providing a structured framework for analysis while dramatically improving measurement precision through localized detection.
3Manufacturing precision
If spatial mapping of HLA variants and tumor antigens is performed, then treatment precision is improved, but device complexity increases due to multiple probes and sequencing steps
Solution Approach 1:
The patent employs universal probes that can detect multiple different HLA variants and tumor antigens simultaneously within the same spatial mapping framework. These multi-functional probes reduce the need for separate detection systems for each target, thereby simplifying the overall device complexity while maintaining high targeting precision. The universal probe design allows a single sequencing and analysis pipeline to handle diverse targets, reducing the number of separate operational steps required.
4Loss of information
If multiple probes for different genes are used to detect antigens, inflammatory markers, and cell typing markers, then information completeness is improved, but difficulty of detecting and measuring increases
Solution Approach 1:
The patent merges the detection of multiple targets (tumor antigens, inflammatory markers, cell typing markers, and HLA variants) into a single integrated spatial mapping process using universal probes. By combining multiple detection functions into one unified approach, the method achieves information completeness for all targets simultaneously while reducing the difficulty of detection. The merged approach allows parallel analysis of all markers within the same experimental framework, eliminating the need for separate detection assays and simplifying data integration.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables more precise targeting of cancer therapies by identifying and addressing clonal populations within tumors, potentially enhancing treatment efficacy by ensuring treatments are directed at expressed antigens and MHC proteins, thereby improving immunotherapy outcomes.
Implementation Method 1
hybridizing a first probe comprising an HLA targeting sequence to the nucleic acid corresponding to the first HLA variant sequence
Data Source
AI summary
The present disclosure provides methods and systems for analyzing a biological sample from a subject, comprising using probes to identify and determine the location of different genetic sequences.