Gut Microbial Composition for ICI/TKI Response Stratification
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Solution Overview
Problem
Current treatments with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for cancer, particularly metastatic renal cell carcinoma (RCC), face challenges in patient stratification and immune-related adverse events, with the intestinal microbiome influencing treatment efficacy but lacking effective predictive markers and therapeutic interventions.
Innovation Solution
Utilizing specific bacterial compositions, such as Alistipes senegalensis, Dorea longicatena, and Eubacterium siraeum, and fecal microbial transplants to modulate the gut microbiota, combined with ICIs and TKIs, to enhance immunostimulation and predict treatment response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors and tyrosine kinase inhibitors are used to treat cancer, then treatment efficacy is improved, but patient stratification difficulty and immune-related adverse events increase
Solution Approach 1:
The patent applies preliminary action by performing metagenomics-based gut oncomicrobiome signature analysis at diagnosis prior to ICI and/or TKI administration to predict treatment response in advance. This allows patient stratification to be performed before treatment begins, enabling clinicians to identify patients likely to respond versus those at risk of adverse events, thereby simplifying the complexity of patient stratification while maintaining treatment efficacy.
2Reliability
If the gut microbiome is analyzed to predict treatment response, then treatment efficacy is improved, but diagnostic complexity increases
Solution Approach 1:
The patent applies the taking out principle by extracting and focusing on specific bacterial taxa and metagenomic features from the complex gut microbiome that are most predictive of treatment response. Rather than analyzing the entire microbiome complexity, the invention identifies and measures specific oncomicrobiome signatures that correlate with ICI and/or TKI efficacy, thereby simplifying the diagnostic process while maintaining prediction accuracy.
3Reliability
If bacterial compositions are used to modulate gut microbiota, then treatment response is improved, but treatment protocol complexity increases
Solution Approach 1:
The patent applies the intermediary principle by introducing specific bacterial compositions as mediators between the patient's gut microbiome and the cancer treatment. These bacterial compositions serve as intermediaries that modulate the gut microbiota to enhance ICI and/or TKI efficacy and reduce adverse events. The standardized bacterial compositions provide a controlled intermediary approach rather than requiring complex personalized microbiome reconstruction.
Data Source
AI summary
The invention pertains to the use of bacteria selected amongst Alistipes senegalensis, Dorea longicatena and Eubacterium siraeum for inducing immunostimulation in a patient in combination with an anti-cancer immunotherapy with an immune check-point inhibitor (ICI) and/or a tyrosine kinase inhibitor (TKI). The invention also relates to methods for assessing the probability that N a patient respond to a treatment with an ICI and/or a TKI, based on measuring the relative abundances of immunotolerant bacterial species (Clostridium hathewayi, Clostridium clostridioforme and Clostridium boltae) and/or immunostimulatory bacterial species CN (Akkermansia muciniphila, Bacteroides salyersiae, Alistipes senegalensis, Dorea longicatena and Eubacterium siraeum) in the patient's gut microbiota.