CRISPR Bacteriophage Delivery for Bladder Cancer Microbiome Modulation
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Solution Overview
Problem
Current cancer treatments, particularly for bladder cancer, face challenges in effectively addressing cancer-related issues such as recurrence, cachexia, and the impact of aging on the immune system, with limited options for enhancing the gut microbiome to prevent infections and cancer progression.
Innovation Solution
A method employing a CRISPR system to selectively kill or reduce pathogenic bacteria like E. coli, Pseudomonas aeruginosa, and Klebsiella, followed by administration of immune checkpoint inhibitors, and enhancing beneficial bacteria like Akkermansia, Bifidobacterium, and Roseburia in the gut microbiome to modulate the immune response and produce therapeutic compounds like p53 protein and tomatidine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments are used, then cancer can be treated, but the immune system's ability to combat cancer is insufficient and recurrence occurs
Solution Approach 1:
The patent introduces beneficial bacteria (Lactobacillus, Bifidobacterium, Akkermansia, etc.) as intermediary agents that modulate the gut microbiome to enhance immune system response. These bacteria act as mediators between the administered therapy and the host immune system, improving cancer treatment effectiveness through immune modulation rather than direct anti-cancer activity.
Solution Approach 2:
The patent changes the composition and diversity parameters of the gut microbiome by introducing specific beneficial bacterial strains. This parameter change in the microbiome ecosystem leads to improved immune system function and enhanced cancer treatment outcomes, addressing the insufficiency of conventional treatments.
2Reliability
If the gut microbiome is not enhanced, then pathogenic bacteria can cause infections, but adding beneficial bacteria requires complex intervention
Solution Approach 1:
The patent employs multiple beneficial bacterial strains (Lactobacillus, Bifidobacterium, Akkermansia muciniphila, Roseburia, Faecalibacterium prausnitzii) that perform multiple functions: they compete with pathogenic bacteria for resources and attachment sites, produce antimicrobial substances, modulate immune responses, and enhance gut barrier function. This multi-functional approach provides comprehensive infection prevention through a single microbiome intervention strategy.
3Productivity
If immune checkpoint inhibitors are administered alone, then cancer treatment is simplified, but treatment outcomes are limited without microbiome modulation
Solution Approach 1:
The patent administers beneficial bacteria to modulate the gut microbiome before or concurrent with immune checkpoint inhibitor therapy. This preliminary action of microbiome conditioning prepares the immune system to respond more effectively to the checkpoint inhibitors, enhancing treatment outcomes without requiring complex sequential protocols.
Data Source
AI summary
A method for treating an individual suffering from bladder cancer employs a CRISPR system to selectively kill or reduce the numbers of pathogenic bacteria within the individual and the individual is then administered an immune checkpoint inhibitor. In particular embodiments, the pathogenic bacteria is one of E. coli, Pseudomonas aeruginosa and Klebsiella bacteria, and the checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, dostarlimab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010. Further embodiments include enhancing the growth of a second bacteria in the individual, such bacteria including Akkermansia, Bacteroides, Bifidobacterium, Clostridium, Enterococcus, Fusobacterium, Coprococcus, Lactobacillus, Propionibacterium, Ruminococcus, Veillonella, Prevotella, Escherichia and Streptococcus. The CRISPR system may include Cas9, Cpf1 and Cas3, and may be delivered using a bacteriophage.