Dual-Targeting CAR-T Cells for CD19 Antigen Loss Relapse
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Solution Overview
Problem
Existing CD19-targeted CAR-T cell therapies for B-ALL and lymphoma face challenges with antigen loss variants leading to relapse, and CD22 expression variability complicates alternative strategies like CD22 CAR-T therapy.
Innovation Solution
Development of chimeric antigen receptors (CARs) targeting both BAFF-R and CD19, with specific formats such as tandem or loop configurations, incorporating transmembrane, costimulatory, and CD3 zeta signaling domains, to enhance T cell efficacy against B cell malignancies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CD19-targeted CAR-T cell therapy is used, then treatment efficacy against B-ALL and lymphoma is improved, but relapse occurs due to antigen loss variants
Solution Approach 1:
The CAR-T cell is engineered to express a single CAR that can bind to both BAFF-R and CD19 antigens simultaneously. This multi-targeting capability allows the T cell to recognize and eliminate B cell malignancies regardless of which antigen is present, preventing relapse from antigen loss variants while maintaining treatment efficacy
2Reliability
If CD22 CAR-T cell therapy is used as alternative strategy, then relapse from CD19 antigen loss can be overcome, but CD22 expression density varies and diminishes after therapy
Solution Approach 1:
Instead of using separate CD22 CAR-T cells, the invention targets BAFF-R which is universally expressed on B cell malignancies. The BAFF-R targeted CAR provides consistent antigen recognition without the expression variability and diminution problems associated with CD22, while still overcoming CD19 antigen loss relapse
Data Source
AI summary
Chimeric antigen receptors targeting both BAFF-R and CD19 are described as are methods for their use.