Cancer Immunotherapy Selection via Interferon Pathway Mutation Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immunotherapies, such as anti-PD-1 therapy, face challenges due to rare genetic mutations in the interferon receptor signaling pathway that lead to innate resistance, as these mutations result in lack of PD-L1 upregulation upon interferon exposure, making it difficult to select appropriate treatment strategies for patients unlikely to respond to immunotherapies.
Innovation Solution
A method is developed to determine the mutation status of cancer using next-generation sequencing, identifying loss of function mutations in the interferon signaling pathway or MHC class I antigen presentation pathway, allowing for the selection of either immune checkpoint therapy or alternative therapies like type I interferon therapy or NK cell activating therapy based on mutation presence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy is administered to treat cancer, then treatment efficacy is improved for most patients, but treatment fails for patients with loss of function mutations in interferon signaling pathway or MHC class I antigen presentation pathway
Solution Approach 1:
The patent performs preliminary genetic testing to detect loss of function mutations in interferon signaling pathway (JAK1, JAK2, IFNGR1, IFNGR2, STAT1, STAT3, STAT5, TYK2) or MHC class I antigen presentation pathway (B2M, HLA-A, HLA-B, HLA-C) before administering immunotherapy. This advance detection allows clinicians to identify patients who will not respond to immunotherapy and select alternative treatments, thereby improving overall treatment reliability and reducing treatment failure rates.
2Productivity
If immunotherapy is administered without genetic testing, then treatment can be started promptly, but patients with resistance mutations receive ineffective treatment wasting time and resources
Solution Approach 1:
The patent implements preliminary genetic testing using next-generation sequencing to detect resistance mutations before immunotherapy initiation. Although this adds a preliminary step, it prevents wasting time on ineffective treatments for mutation-positive patients, ultimately accelerating the time to effective treatment by avoiding treatment failures and enabling rapid selection of appropriate alternative therapies.
3Reliability
If genetic testing is performed to identify resistance mutations, then appropriate treatment selection is improved, but testing complexity and cost increase
Solution Approach 1:
The patent utilizes next-generation sequencing technology to create comprehensive genetic profiles of tumor samples, copying and analyzing the entire relevant genome sequence to identify resistance mutations. This high-throughput sequencing approach efficiently detects mutations in multiple genes simultaneously (JAK1, JAK2, IFNGR1, IFNGR2, STAT1, STAT3, STAT5, TYK2, B2M, HLA-A, HLA-B, HLA-C), providing accurate treatment selection guidance without requiring complex manual testing procedures for each gene individually.
Data Source
AI summary
Disclosed herein are methods of treating or assessing cancer in a subject wherein it has been determined whether the cancer comprises a loss of function mutation or disruption in an immune pathway. The loss of function mutation or disruption can be in JAK1 or JAK2. The loss of function mutation or disruption can be in B2M. The methods can include administering an immune checkpoint therapy such as anti-PD1 or anti-PDL1. The methods can include administering an alternative therapy to an immune checkpoint therapy. In some aspects, the method includes determining whether the cancer comprises a loss of function mutation or disruption in an immune pathway.