Chimeric Antigen Receptor Vector for Multi-Target Tumor Therapy
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Solution Overview
Problem
Current chimeric antigen receptor-engineered T cell therapies (CART) for treating tumors often face limitations in targeting multiple antigens simultaneously, leading to potential antigen escape and reduced efficacy over time.
Innovation Solution
A nucleic acid molecule expressing two or more types of chimeric antigen receptors, each with distinct antigen-binding domains and co-stimulatory domains, is designed to enhance targeting capabilities and reduce antigen escape by using LoxP sites and cleavable peptides for efficient expression and transfection, allowing for dual or triple targeting of tumor antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If single-target CART therapy is used, then the treatment is simpler and easier to implement, but the risk of antigen escape and disease recurrence increases
Solution Approach 1:
The patent divides the targeting function into multiple independent antigen-binding domains within a single CAR structure. Each domain targets a different tumor antigen (e.g., CD19, CD22), allowing the T cell to recognize and attack tumor cells through multiple pathways simultaneously, thereby preventing antigen escape while maintaining a single therapeutic intervention
Solution Approach 2:
The engineered CAR structure serves multiple functions: it contains multiple antigen-binding domains for recognizing different tumor antigens, co-stimulatory domains for T cell activation, and signaling domains for cytotoxicity. This multi-functional design enables a single CART therapy to achieve both broad targeting and effective tumor cell killing
2Adaptability or versatility
If multiple chimeric antigen receptors are expressed in a single vector, then the targeting capability against multiple antigens is enhanced, but the device complexity increases
Solution Approach 1:
The patent merges multiple antigen-binding domains, co-stimulatory domains, and signaling domains into a single integrated chimeric antigen receptor construct. This unified structure is encoded by one nucleic acid sequence and can be delivered via a single viral vector, simplifying the manufacturing process while maintaining the ability to target multiple antigens simultaneously
Solution Approach 2:
The CAR structure employs a nested organization where antigen-binding domains are embedded within the overall CAR architecture, along with co-stimulatory and signaling domains. This hierarchical arrangement allows multiple functional elements to be compactly organized within a single gene construct, reducing vector complexity while preserving multi-targeting capability
Data Source
AI summary
Provided are a vector genetically engineered with a chimeric antigen receptor and against two or more targets for combined treatment of disease such as human tumors, a related immune cell and application thereof. The vector genetically engineered with a chimeric antigen receptor and the related immune cell have enhanced ability to kill target cells.