Humanized CD7 CAR-T Receptor Design for Tumor Immune Evasion
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Solution Overview
Problem
Current CAR-T cell therapies for T-cell lymphomas and leukemias are slow and lacking in development, with existing chimeric antigen receptors (CARs) facing challenges in effectively targeting CD7 molecules, which are highly expressed in these tumors, and the tumor microenvironment affecting therapeutic efficacy.
Innovation Solution
A CD7-based humanized chimeric antigen receptor is developed, comprising an antigen binding domain, transmembrane domain, costimulatory signaling region, and CD3ζ signaling domain, with specific humanized gene modifications to enhance binding and expression, using a nucleotide sequence with high homology to SEQ ID NO. 1-8, and incorporating a self-destructing caspase 9 domain for controlled activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR-T cell therapy is used for T-cell lymphomas and leukemias, then treatment can be provided, but therapeutic efficacy is limited and development is slow
Solution Approach 1:
The patent applies parameter changes by humanizing the CD7 scFv antibody structure and optimizing the CAR construct design to improve therapeutic efficacy while accelerating development through rational design approaches
2Reliability
If existing CAR targets are used, then immune response is activated, but tumor cells can escape through single target immune mechanism
Solution Approach 1:
The patent implements multi-functionality by designing a dual-target CAR construct that simultaneously targets CD7 and CD5 molecules, enabling the CAR-T cells to recognize and eliminate tumor cells through multiple pathways while reducing the risk of immune evasion
3Reliability
If CD7-based CAR is constructed, then specific targeting of T-cell tumors is achieved, but complexity of CAR structure increases
Solution Approach 1:
The patent applies segmentation by dividing the complex dual-target CAR into modular functional domains including CD7 scFv, CD5 scFv, hinge regions, transmembrane domains, and signaling domains, allowing for systematic construction and optimization while managing structural complexity
Data Source
AI summary
The present application relates to a CD7-based humanized chimeric antigen receptor and use thereof, specifically a method for constructing chimeric antigen receptor T (CAR-T) cells based on a tumor-specific target CD7 and use thereof in anti-tumor therapy. The chimeric antigen receptor includes an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3ζ signaling domain, which are connected in tandem; where the antigen binding domain binds to a tumor surface antigen, and the tumor surface antigen is CD7. The humanized chimeric antigen receptor of the present application performs particular gene modification on a single-chain antibody specific to an antigen CD7. The modified humanized single-chain antibody has a stronger antigen-antibody binding ability, and the chimeric antigen receptor stimulates T cells better, is maintained longer in vivo, and has a better targeting effect than other CD7 chimeric antigen receptors so that the therapeutic effect of CAR-T cells is enhanced.