Oligonucleotide Agents Modulate Immune Suppression Genes
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Solution Overview
Problem
Current cancer immunotherapies face challenges with immune checkpoint inhibitors, which can lead to autoimmune side effects and inflammatory toxicity in multiple organ systems, necessitating the development of new therapeutic agents that can be used in combination without these adverse effects.
Innovation Solution
The use of oligonucleotide agents to modulate the expression of target genes involved in immune suppression mechanisms in therapeutic cells, such as TILs and dendritic cells, to inhibit immune resistance pathways, thereby enhancing the efficacy of immunotherapies while minimizing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint inhibitors are used to enhance immunotherapy efficacy, then tumor cell destruction is improved, but autoimmune side effects and inflammatory toxicity occur in multiple organ systems
Solution Approach 1:
The patent segments the immune resistance problem into multiple target genes (PD-L1, CTLA-4, TGF-β, IDO, ARG1, etc.) and uses specific oligonucleotide agents to silence each gene individually or in combination. This segmented approach allows targeted inhibition of immune resistance mechanisms while avoiding the broad immune activation that causes autoimmune side effects with checkpoint inhibitors.
Solution Approach 2:
The patent uses oligonucleotide agents (siRNA, antisense oligonucleotides, miRNA) as intermediary molecules to silence target genes involved in immune resistance. These oligonucleotides act as mediators that specifically bind to mRNA of target genes, preventing protein synthesis without directly activating the immune system, thus avoiding autoimmune reactions while still enhancing immunotherapy efficacy.
2Reliability
If multiple immune resistance mechanism inhibitors are combined to overcome tumor resistance, then therapeutic efficacy is improved, but toxicity increases
Solution Approach 1:
The patent merges multiple gene silencing functions into a single oligonucleotide agent that can target multiple immune resistance genes simultaneously. This is achieved through designing oligonucleotides with multiple binding sites or using combination therapies where several oligonucleotide agents are administered together, each targeting a specific gene. This approach consolidates multiple therapeutic effects while maintaining controlled toxicity through targeted action.
Solution Approach 2:
The patent employs composite oligonucleotide structures that combine different functional elements within a single molecule. These composite oligonucleotides may include multiple silencing sequences, chemical modifications for stability, and targeting moieties, creating a multifunctional therapeutic agent that addresses multiple immune resistance mechanisms simultaneously with improved efficacy and controlled toxicity profile.
Data Source
AI summary
Immunogenic modulators and compositions comprising oligonucleotide agents capable of inhibiting suppression of immune response by reducing expression of one or more gene involved with an immune suppression mechanism.