EPHB4-Targeted CAR-T Cells for Solid Tumor Therapy
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Solution Overview
Problem
There is a lack of sufficient research and clinical application of CAR-T cell therapies in the solid tumor area, particularly for neuroblastoma and osteosarcoma, necessitating a therapeutic strategy to advance CAR therapy in this domain.
Innovation Solution
Development of EPHB4-targeted CAR-T cells by constructing a chimeric antigen receptor (CAR) that includes an EphrinB2 extracellular domain to specifically recognize and target EPHB4-expressing tumor cells, leveraging the natural ligand binding of EphrinB2 to EPHB4 for enhanced cytotoxic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR-T cell therapy is applied to solid tumors, then the general CAR-T mechanism is established, but the therapeutic effect on solid tumors like neuroblastoma and osteosarcoma is insufficient
Solution Approach 1:
The patent applies local quality by using a single-chain antibody (scFv) that specifically targets EPHB4 antigen, which is highly expressed in solid tumors like neuroblastoma and osteosarcoma. This localized targeting approach enhances the therapeutic effect specifically in these tumor types while maintaining the general CAR-T mechanism. The scFv domain is designed to recognize and bind to EPHB4 with high affinity, providing tumor-specific cytotoxic activity.
2Device complexity
If a single-chain antibody is used as the extracellular domain of CAR, then the CAR structure is simplified, but the binding affinity and specificity for tumor antigens may be reduced
Solution Approach 1:
The patent applies parameter changes by optimizing the single-chain antibody (scFv) sequence and structure to enhance binding affinity for EPHB4 antigen. The scFv is engineered with specific amino acid sequences that improve its binding characteristics while maintaining the simplified single-chain structure. This allows the CAR to achieve high binding affinity without requiring complex multi-domain constructions.
3Measurement precision
If CAR-T cells are designed to target highly specific tumor antigens like EPHB4, then the specificity of tumor recognition is improved, but the适用范围 (scope of application) may be limited to specific tumor types
Solution Approach 1:
The patent applies universality by designing a CAR-T cell platform that targets EPHB4, an antigen that is highly expressed across multiple solid tumor types including neuroblastoma, osteosarcoma, and other EPHB4-positive tumors. This approach provides both high specificity for EPHB4-expressing tumors and broad applicability across different solid tumor types that share this antigen expression pattern, achieving multi-functionality in tumor targeting.
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 EPHB4-targeted CAR-T cells demonstrate a potent cytocidal effect on tumors highly expressing EPHB4, confirming the strategy's effectiveness in killing cancer cells and showing promise for treating various solid tumors.
Implementation Method 1
the extracellular domain of the CAR binds to EPHB4 (Ephrin type-B receptor 4)
Data Source
AI summary
An object of the present invention is to provide a therapeutic strategy in the solid tumor area and a means useful therefor to further advance the clinical application of CAR therapy. There is prepared a gene-modified lymphocyte which expresses a chimeric antigen receptor having an EphrinB2 extracellular domain at the antigen recognition site.