Dual-Specific CAR Targeting CD19 and CD22
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Solution Overview
Problem
Current cancer treatments, particularly for hematological malignancies, face challenges in effectiveness due to cancer cells' ability to evade immune recognition by altering antigen expression, leading to poor prognosis and relapse in some patients.
Innovation Solution
Development of a dual-specific chimeric antigen receptor (CAR) with antigenic specificity for both CD19 and CD22, comprising an anti-CD22 antigen binding domain, an anti-CD19 antigen binding domain, a hinge domain, a transmembrane domain, and an intracellular T cell signaling domain, to redirect T-cell specificity and enhance immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single-antigen CAR is used, then the treatment is simpler and more specific, but cancer cells can escape by altering that single antigen expression
Solution Approach 1:
The patent applies multi-functionality by designing a CAR that performs multiple antigen recognition functions simultaneously. The dual-specific CAR contains both anti-CD19 and anti-CD22 binding domains, enabling a single receptor to target multiple antigens on cancer cells, thereby preventing escape mechanisms while maintaining treatment effectiveness.
Solution Approach 2:
The invention merges two separate antigen-specific binding domains (anti-CD19 and anti-CD22) into a single chimeric antigen receptor molecule. This combining allows the CAR to recognize and bind to cancer cells expressing either antigen, eliminating the need for separate CAR therapies and reducing the risk of antigen loss-mediated escape.
2Reliability
If dual-specific CAR is used, then cancer cell escape mechanisms are reduced, but the receptor structure becomes more complex
Solution Approach 1:
The dual-specific CAR is segmented into distinct functional domains: an anti-CD19 binding domain, an anti-CD22 binding domain, a hinge domain, a transmembrane domain, and an intracellular signaling domain. This segmentation allows each domain to perform its specific function while maintaining an organized and manageable overall structure that can be engineered and expressed effectively.
3Productivity
If dual-specific CAR is used, then treatment potency increases, but the manufacturing and characterization become more difficult
Solution Approach 1:
The patent employs preliminary action by pre-optimizing the dual-specific CAR sequence and structure before clinical application. The specific amino acid sequences for the anti-CD19 and anti-CD22 binding domains are predetermined and engineered to ensure proper folding, stability, and function, thereby facilitating smoother manufacturing and characterization processes despite the increased complexity.
Data Source
AI summary
The invention provides dual specific chimeric antigen receptors (CARs) having antigenic specificity for CD19 and CD22. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.