Dual CD19/CD22 CAR Constructs for Persistent B-Cell Targeting
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Solution Overview
Problem
Current treatments for B cell malignancies are often ineffective and associated with serious side effects, and existing CAR-T cell therapies face challenges in achieving long-term persistence and functionality.
Innovation Solution
Development of dual CAR molecules that combine a CD22 CAR and a CD19 CAR, each with specific antigen binding domains, transmembrane domains, co-stimulatory signaling domains, and primary signaling domains, to enhance targeting and activation of immune cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional treatment options are used for B cell malignancies, then treatment can be administered, but clinical effectiveness is poor and serious side effects occur
Solution Approach 1:
The patent replaces traditional chemical chemotherapy mechanisms with a biological immune system mechanism. CAR-T cells are engineered to express chimeric antigen receptors that specifically recognize and bind to CD19 or CD22 on B cell malignancies, enabling targeted destruction of cancer cells through immune-mediated mechanisms rather than non-specific chemical cytotoxicity
Solution Approach 2:
The patent introduces engineered CAR-T cells as an intermediary between the patient's immune system and the B cell malignancy. These genetically modified T cells serve as a bridge that redirects immune specificity toward cancer cells expressing CD19 or CD22, enabling precise targeting while sparing healthy tissues from the harmful effects of traditional chemotherapy
2Reliability
If single CAR-T cell therapy is used, then T cells can be redirected to target cancer cells, but long-term persistence and functionality are compromised
Solution Approach 1:
The patent segments the targeting function into two distinct CAR variants: one targeting CD19 and another targeting CD22. These segmented CAR-T cell populations can be used individually or in combination, allowing the immune system to maintain persistent anti-tumor activity through diverse antigen recognition pathways that complement each other over time
Solution Approach 2:
The patent changes the antigen specificity parameter by providing two different CAR variants with different antigen binding domains (anti-CD19 vs anti-CD22). This parameter diversification enables the T cell population to persist longer by reducing antigen escape and maintaining functional activity through alternative recognition pathways when one antigen becomes less available
3Adaptability or versatility
If tumor antigens are derived from self, then they can be identified, but immunogenicity is poor making immune attack difficult to initiate
Solution Approach 1:
The patent substitutes the natural immune recognition mechanism (which fails to respond strongly to self-derived tumor antigens) with an engineered receptor system. The chimeric antigen receptors are artificially designed to recognize CD19 or CD22 with high affinity and specificity, bypassing the need for natural immunogenicity and enabling reliable immune attack initiation against B cell malignancies
Data Source
AI summary
The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and/or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and/or CD19, methods of making a cell comprising the same and vectors encoding the same.