Gut Microbial Compositions for Checkpoint Inhibitor Response
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Solution Overview
Problem
Existing cancer therapies, particularly checkpoint inhibitor immunotherapies, have limited effectiveness due to variations in gut microbiome composition, with more than 50% of patients not responding effectively, as certain gut microbes influence immunological function and T-cell activation.
Innovation Solution
Administering combinations of non-pathogenic, live bacteria and bacterial spores to modulate the gut microbiome, enhancing the pharmacodynamics of cancer drugs and improving the efficacy of therapies like chemotherapy, radiation therapy, and immune checkpoint inhibitors by modifying gut microbial populations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint inhibitor immunotherapy is administered to treat cancer, then T-cell activation and cancer rejection are enhanced, but more than 50% of patients do not respond effectively due to variations in gut microbiome composition
Solution Approach 1:
The patent introduces specific gut microbes (Bifidobacterium longum, Faecalibacterium prausnitzii, Akkermansia muciniphila) as intermediary agents that mediate between the checkpoint inhibitor therapy and the patient's immune system. These microbial compositions act as biological mediators that prime T-cells and enhance their responsiveness to PD-1/PD-L1 blockade, thereby improving treatment reliability across patients with different baseline microbiomes.
Solution Approach 2:
The patent modifies the gut microbiome composition parameter by administering specific probiotic bacteria and spores. This changes the microbiome state from a variable, unpredictable composition to a controlled, optimized composition enriched with immunomodulatory species, thereby standardizing the immune response to checkpoint inhibitors across different patients.
2Reliability
If higher doses of cancer drugs are administered to improve treatment efficacy, then dose efficacy increases, but drug toxicity increases
Solution Approach 1:
The gut microbial composition acts as an intermediary that enhances drug-pharmacodynamic interactions. By optimizing the microbiome, the patent creates a biological environment that increases the efficacy of standard drug doses, allowing lower doses to achieve the same therapeutic effect, thereby reducing toxicity while maintaining or improving dose efficacy.
3Reliability
If chemotherapy or radiation therapy is administered to treat cancer, then tumor control is achieved, but gut microbiome composition is disrupted leading to reduced immunotherapy response
Solution Approach 1:
The patent administers the microbial composition before chemotherapy or radiation therapy to establish a resilient, immunomodulatory microbiome baseline. This preliminary action protects the gut microbiome from treatment-induced disruption and maintains T-cell priming capacity throughout the course of cytotoxic therapy, ensuring subsequent immunotherapy effectiveness.
Solution Approach 2:
The probiotic and spore-forming bacterial compositions serve as a protective cushion against the harmful effects of chemotherapy and radiation on the gut microbiome. By pre-establishing populations of beneficial microbes, the patent creates a buffer that absorbs the disruptive impact of cytotoxic treatments and maintains microbiome stability.
Data Source
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AI summary
Provided are compositions, including products of manufacture and kits, and methods, comprising combinations of microbes, such as non-pathogenic, live bacteria and/or bacterial spores, for the control, amelioration, prevention, and treatment of a disease or condition, for example, a cancer. In alternative embodiment, these non-pathogenic, live bacteria and/or bacterial spores are administered to an individual in need thereof, thereby resulting in a modification or modulation of the individual's gut microfloral population(s). In alternative embodiments, by modulating or modifying the individual's gut microbial population(s) using compositions, products of manufacture and methods as provided herein, the pharmacodynamics of a drug administered to the individual is altered, thereby controlling, ameliorating, preventing and/or treating of that cancer. Combinations of microbes are administered with chemotherapy, radiation therapy, an immune checkpoint inhibitor, a Chimeric Antigen Receptor T-cell therapy or other immunotherapy or cancer treatment.