Microbiome Analysis for Predicting CAR T Cell Therapy Response
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Solution Overview
Problem
Current CAR T cell therapies face challenges in predicting patient response, with existing methods failing to effectively identify individuals likely to have a poor response, leading to variable treatment outcomes.
Innovation Solution
Analyzing the intestinal microbiome to determine the levels of specific bacteria and genes, such as those from the Peptostreptococcaceae, Bacteroidaceae, and Lachnospiraceae families, and genes involved in vitamin B biosynthesis and secondary bile acid biosynthesis, to predict patient response to CAR T cell therapy, and administering therapeutic bacteria or pharmaceuticals to improve treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional CAR T cell therapy is administered without microbiome analysis, then treatment can be provided to all patients, but the ability to predict patient response is poor and treatment outcomes are variable
Solution Approach 1:
The patent performs microbiome analysis before administering CAR T cell therapy to predict patient response. By analyzing bacterial levels (such as Peptostreptococcaceae, Bacteroidaceae, Lachnospiraceae families) and genetic markers in advance, the system identifies patients likely to have poor responses and administers prebiotics or probiotics beforehand to modify the microbiome, thereby improving subsequent therapy effectiveness.
Solution Approach 2:
The patent introduces microbiome components (prebiotics, probiotics, or fecal microbiota transplantation) as intermediaries between the patient's existing microbiome and the CAR T cell therapy. These microbiome modulators serve as mediators that can improve T cell function and therapy outcomes by altering the gut microbiota composition prior to or during treatment.
2Reliability
If microbiome analysis is performed to identify patients at risk of poor response, then personalized treatment prediction is achieved, but the complexity of the diagnostic process increases
Solution Approach 1:
The patent extracts specific bacterial taxa and genetic markers from the complex microbiome that are most predictive of CAR T cell therapy response. By focusing on key indicators such as levels of specific bacterial families (Peptostreptococcaceae, Bacteroidaceae, Lachnospiraceae) and their genetic signatures, the system simplifies the diagnostic process while maintaining high predictive reliability.
Solution Approach 2:
The patent changes the measurement parameters from comprehensive microbiome sequencing to targeted quantification of specific bacterial markers and genetic sequences. This parameter change enables more straightforward detection and measurement while preserving the ability to reliably predict therapy response.
3Productivity
If therapeutic bacteria or prebiotics are administered to modify microbiome, then CAR T cell therapy response is improved, but the treatment protocol becomes more complex
Solution Approach 1:
The patent administers prebiotics, probiotics, or fecal microbiota transplantation before CAR T cell therapy to pre-condition the patient's microbiome for better therapy response. This preliminary microbiome modulation creates a more favorable environment for T cell function and reduces the risk of poor outcomes.
Solution Approach 2:
The patent maintains continuous microbiome modulation throughout the treatment process, administering therapeutic bacteria or prebiotics both before and during CAR T cell therapy. This continuous intervention ensures sustained microbiome benefits that support T cell function throughout the therapeutic course.
Data Source
AI summary
The present invention relates to compositions, methods, and kits for predicting a subject's response to a CAR T cell therapy, by analyzing the intestinal microbiome of the subject. The present disclosure also provides a method of detecting patients at risk for a poor response to CAR T cell therapy by measuring the level of the presently disclosed bacteria or bacterial genes in the microflora or microbiome of a patient receiving or considered for CAR T cell therapy. The present disclosure further provides therapeutic compositions and methods for treating a subject having a cancer, by improving the subject's response to a CAR T cell therapy.