Humanized CD19 CAR for Lower-Immunogenicity Allogeneic CAR-T
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Solution Overview
Problem
Existing CD19-targeting chimeric antigen receptor (CAR) technologies face issues such as immunogenicity, leading to rapid elimination of CAR-T cells and disease relapse, and are limited by complex and expensive individualized preparation processes with significant toxic effects.
Innovation Solution
Development of a nucleic acid molecule encoding a chimeric antigen receptor targeting CD19 with specific antigen-binding regions and intracellular domains, reducing immunogenicity and enabling the use of allogeneic immune effector cells for treating CD19-related tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a murine antibody FMC63 is used for the CAR-T product, then the CAR-T cells can specifically bind to CD19, but the immunogenicity increases causing rapid elimination of CAR-T cells and disease relapse
Solution Approach 1:
The patent applies parameter changes by modifying the antibody sequence parameters - specifically humanizing the murine FMC63 antibody to create a chimeric antibody with reduced immunogenicity while maintaining CD19 binding capability. This involves changing the amino acid sequence parameters of the antibody to match human immunoglobulin structures, thereby reducing the immune response against the CAR-T cells.
2Adaptability or versatility
If individualized CAR-T cell therapy is prepared for each patient, then the treatment can be tailored to the patient's specific condition, but the preparation process becomes complex and expensive
Solution Approach 1:
The patent applies universality by developing a standardized chimeric antibody sequence that can be used across multiple patients. The humanized FMC63 antibody sequence serves as a universal component that can be incorporated into CAR constructs for different patients without requiring individual customization, thereby simplifying the preparation process while maintaining therapeutic effectiveness.
3Reliability
If CAR-T cell therapy is administered to patients, then anti-tumor activity is achieved, but significant toxic effects including cytokine release syndrome and neurotoxicity occur
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's amino acid sequence parameters through humanization. This reduces the immunogenicity of the CAR-T cells, which in turn decreases the severity of toxic effects such as cytokine release syndrome and neurotoxicity, while preserving the anti-tumor activity through maintained CD19 specificity.
Data Source
AI summary
Provided are a CD19-targeting chimeric antigen receptor and use thereof. Further provided are a CD19-targeting chimeric antigen receptor, a corresponding nucleic acid molecule, a vector, an immune effector cell, a preparation method therefor, a product thereof, a pharmaceutical composition, a therapeutic use, a pharmaceutical use, and a tumor or cancer treatment method.