RIP2 Inhibitor–ICI Combination for Tumor Immune Sensitization
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Solution Overview
Problem
Existing immune checkpoint inhibitors (ICIs) for tumor treatment exhibit low response rates, strong cytotoxicity, and treatment resistance, limiting their effectiveness in clinical applications.
Innovation Solution
A pharmaceutical composition combining a receptor-interacting protein 2 (RIP2) inhibitor, such as GSK583, with an ICI, like pembrolizumab or atezolizumab, to enhance the therapeutic efficacy of ICIs by up-regulating CD3+ cells, CD8+ T cells, and other immune cell populations in the tumor microenvironment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors (ICIs) are used for tumor treatment, then anti-tumor activity is improved, but response rate remains low (5-30%)
Solution Approach 1:
The patent combines RIP2 inhibitor with immune checkpoint inhibitor (ICI) to create a synergistic therapeutic approach. The RIP2 inhibitor modifies the tumor microenvironment and enhances T cell infiltration, while the ICI blocks checkpoint pathways, together achieving higher response rates than ICI alone.
Solution Approach 2:
The patent changes the immunological parameters of the tumor microenvironment by inhibiting RIP2 signaling, which alters the balance of immune cell populations and cytokine profiles, thereby increasing sensitivity to ICI therapy and improving response rates.
2Reliability
If immune checkpoint inhibitors (ICIs) are used for tumor treatment, then anti-tumor activity is improved, but cytotoxicity increases
Solution Approach 1:
The RIP2 inhibitor acts as an intermediary that modifies the tumor microenvironment to reduce immunosuppression and enhance immune cell function. This intermediary approach allows lower doses of ICI to achieve the same therapeutic effect, thereby reducing cytotoxicity while maintaining anti-tumor activity.
3Reliability
If immune checkpoint inhibitors (ICIs) are used for tumor treatment, then anti-tumor activity is improved, but treatment resistance develops
Solution Approach 1:
The RIP2 inhibitor is administered to preliminarily modify the tumor microenvironment and enhance immune cell infiltration before ICI treatment. This preliminary action prepares the tumor bed to be more responsive to ICI, preventing the development of resistance and sustaining long-term anti-tumor activity.
Data Source
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AI summary
Disclosed are a pharmaceutical composition of a receptor-interacting protein 2 (RIP2) inhibitor in combination with an immune checkpoint inhibitor and use thereof. The present invention provides a pharmaceutical composition comprising an RIP2 inhibitor and an immune checkpoint inhibitor (ICI). Particularly, the present invention provides use of the RIP2 inhibitor in combination with the ICI in the preparation of a medicament for treating and/or preventing tumors. The knockout of the RIP2 or the RIP2 inhibitor has a new application of increasing the sensitivity of tumors to the ICI, i.e., has the effect of enhancing the anti-tumor activity of an ICI medicament. According to the present invention, the anti-tumor activity of an ICI medicament can be enhanced by knocking out the RIP2 or using the RIP2 inhibitor for the first time. After the RIP2 inhibitor and the ICI are jointly used, the proportions of CD3+ cells, CD8+ T cells, γδTCR+ T cells, effector memory T cells, and CD8 effector T cells (IFNγ+ CD8+ T cells, Granzyme B+ CD8+ T cells, TNFα+ CD8+ T cells, and CD107a+ CD8+ T cells) in a tumor microenvironment are up-regulated, and the therapeutic effect of the ICI medicament on tumors is enhanced.