Bispecific CAR-T Cells Targeting CD19 and CD20
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Solution Overview
Problem
Current CAR-T cell therapies targeting CD19 for treating B-cell malignancies face challenges with antigen escape, leading to relapse in patients, as tumor cells can down-regulate or lose CD19 expression, limiting treatment efficacy.
Innovation Solution
Development of a bispecific chimeric antigen receptor (CAR) that simultaneously targets CD19 and CD20, combining anti-CD20 and anti-CD19 antigen-binding regions with co-stimulatory signaling domains, to enhance tumor recognition and reduce immune escape.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CD19-targeted CAR-T cell therapy is used to treat B-cell malignancies, then treatment efficacy is improved, but antigen escape occurs leading to relapse
Solution Approach 1:
The CAR-T cell receptor is segmented into two independent antigen-binding domains: one targeting CD19 and another targeting CD20. This segmentation allows the system to recognize and attack tumor cells through multiple antigenic pathways simultaneously, preventing escape through single-antigen downregulation.
Solution Approach 2:
The CAR-T cell is designed with multi-functionality by incorporating dual antigen-specific binding domains (CD19 and CD20). This enables a single CAR-T cell to perform multiple recognition functions against different antigen targets on tumor cells, enhancing therapeutic reliability and preventing antigen escape mechanisms.
2Device complexity
If single-antigen CAR-T cells are used, then treatment simplicity is maintained, but treatment durability is reduced due to relapse
Solution Approach 1:
Two antigen-binding domains (CD19 and CD20) are merged into a single CAR-T cell receptor structure. This merging enables the CAR-T cell to simultaneously recognize and respond to both antigens, extending treatment durability by preventing relapse while maintaining a unified cellular therapy platform.
3Productivity
If CD19 antigen expression is targeted, then initial response rate is high, but relapse rate increases due to antigen loss
Solution Approach 1:
The dual-target CAR-T cell system provides feedback through simultaneous monitoring of CD19 and CD20 antigen expression on tumor cells. If tumor cells downregulate CD19, the CD20-targeting domain provides compensatory recognition, maintaining continuous anti-tumor activity and preventing relapse.
Data Source
AI summary
The present invention provides a combined chimeric antigen receptor targeting CD19 and CD20 and application thereof. Specifically, the present invention provides a combined chimeric antigen receptor targeting CD19 and CD20, which comprises a scFv targeting CD19 and a scFv targeting CD20, a hinge region, a transmembrane region, and an intracellular signaling domain. The present invention provides a nucleic acid molecule encoding the chimeric antigen receptor and a corresponding expression vector, a CAR-T cell, and applications thereof. The experimental results show that the chimeric antigen receptor provided by the present invention shows extremely high killing ability against tumor cells. The chimeric antigen receptor of the present invention targets CD19 and/or CD20 positive cells and can be used to treat CD19 and/or CD20 positive B-cell lymphoma, leukemia and other diseases.