B2M Genotyping for MHC Class I Deficiency Detection
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Solution Overview
Problem
Current immunotherapy approaches, such as cancer immunotherapy, face challenges in effectively targeting cells that lack or have deficient MHC class I expression, leading to resistance and treatment failure, as these cells evade immune detection by presenting antigens inadequately.
Innovation Solution
A method for screening genotypes for loss of antigen presentation via MHC class I by identifying chromosomal deletions and inversions in chromosome 15, specifically targeting the beta-2 microglobulin (B2M) locus, using nucleic acid sequencing and PCR techniques to detect predictive biomarkers for resistance against immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy is applied to treat cancer, then immune response against tumor cells is enhanced, but treatment effectiveness is reduced when target cells lack MHC class I expression
Solution Approach 1:
The patent performs preliminary genotyping to detect chromosomal deletions and inversions in the B2M locus before initiating immunotherapy. This advance detection identifies patients with MHC class I deficiency, allowing clinicians to select alternative treatment strategies before immunotherapy fails, thereby resolving the contradiction between enhancing immune response and ensuring applicability to all patient types.
2Measurement precision
If MHC class I molecules present antigens to T cells, then immune detection of target cells is improved, but cells with MHC class I deficiency evade immune detection
Solution Approach 1:
The patent converts the harmful effect of MHC class I deficiency (immune evasion) into a beneficial diagnostic opportunity. By detecting chromosomal deletions and inversions in the B2M locus, the method identifies cells that would otherwise evade immune detection, allowing clinicians to avoid ineffective immunotherapy and select alternative treatments, thus turning a pathological feature into a useful biomarker.
3Loss of information
If chromosomal deletions and inversions in B2M locus are identified, then patient suitability for immunotherapy is determined, but additional diagnostic steps are required
Solution Approach 1:
The patent extracts and focuses specifically on detecting chromosomal deletions and inversions in the B2M locus as the critical genetic markers for immunotherapy suitability. By concentrating the diagnostic effort on these specific genetic alterations rather than comprehensive genomic analysis, the method obtains essential information about treatment suitability while minimizing diagnostic complexity through targeted detection.
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
Enables the identification of patients unsuitable for immunotherapy due to MHC class I deficiency, allowing for personalized treatment strategies and potentially improving treatment outcomes by avoiding ineffective therapies.
Implementation Method 1
using nucleic acid sequencing and PCR techniques to detect predictive biomarkers for resistance against immunotherapy
Data Source
AI summary
This invention relates to methods for screening for a genotype for loss of antigen presentation via MHC class I in a subject and/or respectively detecting a subject's increased risk of resistance against immunotherapy such as against vaccination.