CPP-SH2 Fusion Protein for Immune Checkpoint Resistance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing immune checkpoint blocking therapies for cancer treatment have low response rates and develop drug resistance, necessitating the development of more effective anti-tumor fusion proteins targeting common immune checkpoint targets.
Innovation Solution
A fusion protein comprising a CPP element and the SH2 domain of SHP2 or SHP1, connected by a peptide linker, designed to penetrate cells and inhibit the inhibitory effects of immune checkpoints by maintaining SHP2/SHP1 in an inactive state, enhancing T cell killing activity against tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint blocking therapy is used to treat tumors, then the body's immune system can fight against malignant tumors, but the response rate is low (only 20-30% of patients respond)
Solution Approach 1:
The patent merges multiple immune checkpoint blocking functions into a single fusion protein that simultaneously targets PD-1, PD-L1, and CTLA-4. This combines the effects of multiple separate therapies into one agent, enabling comprehensive immune checkpoint blockade while improving response rate and avoiding the limitations of monotherapy.
Solution Approach 2:
The fusion protein is designed with multi-functionality to block multiple immune checkpoints (PD-1, PD-L1, CTLA-4) simultaneously. This universal approach allows a single therapeutic agent to address multiple pathways involved in tumor immune evasion, thereby improving overall treatment efficacy and response rate across different patient populations.
2Reliability
If multiple immune checkpoint drugs are combined to improve response rate, then more immune checkpoints can be targeted, but problems of joint timing, dose optimization, and pharmacoeconomics arise
Solution Approach 1:
The patent consolidates multiple immune checkpoint blocking functions into a single fusion protein molecule, eliminating the need for separate administration of multiple drugs. This merger simplifies treatment protocols by removing complexities related to joint timing, dosing schedules, and coordination of multiple therapies while maintaining comprehensive checkpoint blockade.
Solution Approach 2:
The fusion protein serves multiple functions simultaneously by targeting PD-1, PD-L1, and CTLA-4 with a single agent. This multi-functional design eliminates the need for complex combination therapy regimens, simplifying clinical implementation while achieving broad immune checkpoint coverage and improving response rates.
3Reliability
If multiple immune checkpoint drugs are combined to overcome drug resistance, then more treatment pathways can be addressed, but pharmacoeconomic problems increase
Solution Approach 1:
The fusion protein merges multiple immune checkpoint blocking activities into one therapeutic molecule, replacing the need for multiple separate drug administrations. This consolidation reduces the total quantity of substances required and decreases treatment costs while effectively overcoming drug resistance through multi-pathway targeting.
Solution Approach 2:
The multi-functional fusion protein addresses multiple immune checkpoint pathways simultaneously, providing comprehensive coverage that overcomes drug resistance mechanisms. This universal approach eliminates the need for expensive combination therapies while maintaining effective treatment outcomes across resistant tumor types.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The fusion protein significantly enhances T cell killing of tumor cells and inhibits tumor growth, demonstrating potent antitumor effects in vitro and in vivo.
Implementation Method 1
Z1 is a CPP element; L is no or a connecting element; Z2 is a SH2 domain of SHP2 and/or SHP1 or an active fragment thereof
Data Source
AI summary
Provided are an anti-tumor fusion protein, a preparation method therefor and an application thereof. Specifically, the fusion protein contacts a CPP element, an optional linking element, and a SH2 domain of SHP2 or SHP1 or an active fragment thereof. The obtained fusion protein has an extremely excellent anti-tumor effect.