Dual-CAR Cell Targeting CD19 and CD22 to Prevent Tumor Escape
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Solution Overview
Problem
Existing immunotherapeutic agents targeting a single antigen, such as CD19, are susceptible to cancer escape due to antigen modulation and tumour heterogeneity, leading to relapse in CD19-negative cancers.
Innovation Solution
Development of a cell that co-expresses two chimeric antigen receptors (CARs) specific for CD19 and CD22, with distinct spacers and endodomains, allowing simultaneous targeting of both antigens to overcome spatial and accessibility issues and reduce cancer escape.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single antigen target (CD19) is used for CAR therapy, then the treatment is simple and targeted, but tumour escape occurs due to antigen modulation and heterogeneity
Solution Approach 1:
The invention divides the single CAR structure into multiple independent CARs (first CAR and second CAR) that coexist on the same cell. Each CAR targets a different antigen (CD19 and CD22 respectively), allowing the system to segment the targeting function across multiple specificities rather than relying on a single target
Solution Approach 2:
The engineered cell is designed with multi-functionality by co-expressing multiple CARs with different antigen specificities. This allows a single cell type to perform multiple targeting functions simultaneously, adapting to different antigen expressions on tumor cells while maintaining the same effector mechanism
2Reliability
If two CARs with distinct spacers and endodomains are co-expressed, then cancer escape is reduced and treatment efficacy is improved, but device complexity increases
Solution Approach 1:
The invention segments the CAR structure into distinct functional modules (antigen-binding domain, spacer, transmembrane domain, endodomain) that can be independently configured for different antigens. This modular segmentation allows systematic design of multiple CARs while maintaining structural consistency and functional independence
Solution Approach 2:
Different regions of the CAR structure are optimized for specific functions: the antigen-binding domain provides antigen specificity, the spacer provides structural flexibility and orientation, the transmembrane domain provides membrane anchoring, and the endodomain provides signaling. Each region has localized quality tailored to its function, enabling reliable multi-CAR co-expression
Data Source
AI summary
A cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.