Gut Microbiota Modulation for Immune Agonist Antibody Toxicity
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Solution Overview
Problem
Current immunotherapy using immune agonist antibodies often results in significant side effects such as liver damage, cytokine release syndrome, and other immune-mediated adverse events, limiting their clinical application due to dose-limiting toxicities and reduced anti-tumor efficacy.
Innovation Solution
Modifying the gut microbiota in patients undergoing immunotherapy with immune agonist antibodies, either alone or in combination with immune checkpoint inhibitors, to reduce side effects and enhance treatment safety without compromising anti-tumor efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune agonist antibodies are used for cancer immunotherapy, then anti-tumour immunity is enhanced, but immunotoxicity and side effects increase
Solution Approach 1:
The patent introduces gut microbiota as an intermediary mediator between the immune agonist antibody and the host immune system. By modifying the gut microbiota composition, the patent creates a buffering layer that reduces harmful immunotoxicity while preserving the beneficial anti-tumour immune activation. This intermediary approach allows the immune agonist to exert its therapeutic effect without causing excessive systemic inflammation.
Solution Approach 2:
The patent applies parameter changes by altering the composition and diversity of gut microbiota through interventions such as probiotic administration, prebiotic supplementation, or fecal microbiota transplantation. These changes in microbial parameters modulate the immune response to immune agonist antibodies, reducing immunotoxicity while maintaining anti-tumour efficacy.
2Productivity
If higher doses of immune agonist antibodies are administered, then anti-tumour efficacy increases, but dose-limiting toxicity increases
Solution Approach 1:
The patent implements beforehand cushioning by pre-modifying the gut microbiota composition before administering immune agonist antibodies. This preparatory intervention creates a resilient immune system that can tolerate higher doses of therapy without experiencing excessive toxic effects, thereby enabling dose escalation to achieve better anti-tumour responses.
3Reliability
If immune checkpoint inhibitors are combined with immune agonists, then anti-tumour immunity is enhanced, but immune-related adverse events increase
Solution Approach 1:
The patent uses gut microbiota as a mediating factor that regulates the interaction between immune checkpoint inhibitors and immune agonists. By optimizing microbiota composition, the patent enhances the synergistic anti-tumour effect of the combination therapy while buffering against the additive toxic effects, thereby improving the safety profile of combined immunotherapy.
Data Source
AI summary
The present disclosure relates to methods and products for reducing side effects associated with immunotherapy using immune agonist antibodies. In certain embodiments, the present disclosure provides a method of reducing one or more side effects associated with immunotherapy using an immune agonist antibody alone, or in combination with an immune checkpoint inhibitor, in a subject suffering from a cancer, the method comprising modifying the gut microbiota in the subject and thereby reducing the one or more side effects associated with the immunotherapy in the subject.