Cyclic Dinucleotide STING Agonists for Immunosuppression
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Solution Overview
Problem
Current cancer therapies face challenges in effectively activating the STING pathway to enhance antitumor immune responses, as tumor cells often create an immunosuppressive microenvironment that hampers the body's natural tumor-specific T cell responses.
Innovation Solution
Development of STING agonists, including compounds of Formula (I), (II), and (III), and their pharmaceutical compositions, which activate the STING protein to induce type I interferon and cytokine production, thereby enhancing immune responses against cancer and other diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used, then treatment is provided, but the STING pathway is not effectively activated and antitumor immune responses are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of cyclic dinucleotides to create STING agonists with enhanced activity. Specifically, the invention uses non-natural nucleotide bases (such as 2-thiouridine, 2-thioguanine, 5-methyluridine) replacing natural bases to produce compounds with higher affinity for STING and improved immunostimulatory activity, thereby effectively activating the STING pathway and enhancing antitumor immune responses
2Object-affected harmful factors
If tumor cells create an immunosuppressive microenvironment, then cancer development is favored, but natural T cell responses are hampered
Solution Approach 1:
The patent uses STING agonists as intermediary substances that bridge the gap between tumor presence and T cell activation. These agonists act as mediators that trigger the STING pathway, leading to type I interferon production, which in turn creates a pro-inflammatory microenvironment that reverses tumor-induced immunosuppression and enhances T cell responses against cancer cells
Data Source
AI summary
The disclosure provides cyclic dinucleotides that are useful as STING agonists, pharmaceutical compositions and vaccines comprising the cyclic dinucleotides, and methods of treating diseases and disorders using the cyclic dinucleotides, pharmaceutical compositions, and vaccines.