Microbial Composition Modulating Immune Response in Colorectal Cancer
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Solution Overview
Problem
Current treatments for colorectal cancer, particularly those involving immunotherapy, face limitations such as drug resistance and limited efficacy in microsatellite stable tumors, highlighting the need for new methods to enhance therapeutic outcomes.
Innovation Solution
The use of specific gut microbial species like Lactobacillus gallinarum, Roseburia intestinalis, and Streptococcus salivarius K12, combined with metabolites like indole-3-carboxylic acid and butyrate, to enhance the efficacy of immunotherapy by modulating the immune response and suppressing colorectal cancer cell proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy is used to treat colorectal cancer, then anti-cancer immune response is elicited, but drug resistance develops and efficacy is limited
Solution Approach 1:
The patent introduces gut microbiota (Lactobacillus gallinarum, Roseburia intestinalis, Streptococcus salivarius K12) and their metabolites (indole-3-carboxylic acid, butyrate) as intermediary substances that mediate between the immunotherapy agent and the tumor microenvironment. These microbiota components modulate the immune response by reducing regulatory T cell infiltration and enhancing effector T cell function, thereby overcoming drug resistance and improving immunotherapy efficacy in colorectal cancer treatment
2Reliability
If immunotherapy is administered alone, then treatment simplicity is maintained, but therapeutic efficacy is insufficient
Solution Approach 1:
The patent merges immunotherapy with gut microbiota modulation into a combined treatment approach. Specifically, it combines anti-PD1/PDL1 or anti-CTLA4 immunotherapy agents with specific probiotic strains (Lactobacillus gallinarum, Roseburia intestinalis, Streptococcus salivarius K12) and their metabolites. This combination therapy achieves enhanced therapeutic efficacy by synergistically activating immune response while suppressing tumor growth, overcoming the limitations of monotherapy
3Reliability
If regulatory T cells are present in tumor microenvironment, then immune suppression occurs, but removing them requires complex immunomodulation
Solution Approach 1:
The patent employs gut microbiota components (indole-3-carboxylic acid and butyrate) that naturally and selectively modulate the tumor microenvironment by reducing regulatory T cell infiltration. These microbiota-derived metabolites self-service the immune system by enhancing effector T cell function and suppressing immunosuppressive cells without requiring complex external immunomodulation protocols, thereby simplifying the treatment approach while improving immune response
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
These microbial species and metabolites significantly improve the therapeutic efficacy of immunotherapy by reducing regulatory T cell infiltration, enhancing effector T cell function, and inhibiting IDO1 expression, thereby effectively inhibiting colorectal cancer progression.
Implementation Method 1
These microbial species and metabolites significantly improve the therapeutic efficacy of immunotherapy by reducing regulatory T cell infiltration, enhancing effector T cell function, and inhibiting IDO1 expression
Implementation Method 2
These microbial species and metabolites significantly improve the therapeutic efficacy of immunotherapy by reducing regulatory T cell infiltration, enhancing effector T cell function, and inhibiting IDO1 expression
Data Source
AI summary
A composition for use in enhancing efficacy of immunotherapy for colorectal cancer in a subject in need thereof includes an effective amount of (1) any one or more of Lactobacillus gallinarum. Roseburia intestinalis, and Streptococcus salivarius K12; and (2) a physiologically acceptable excipient.