OCTS-Based CAR-T Vector for Dual Antigen Recognition
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current CAR-T therapies face limitations in recognizing multiple tumor antigens simultaneously, leading to rapid tumor recurrence, and require multiple transductions that reduce efficiency and increase the risk of immune evasion by tumor cells.
Innovation Solution
Development of an OCTS-based CAR-T vector that integrates two single-chain antibodies (scFvs) into a chimeric molecule, allowing T lymphocytes to recognize two tumor antigens efficiently, while also incorporating a PDL1 single-chain antibody to block negative control signals and enhance immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If two groups of CARs are transduced into primary T lymphocytes by building them into a lentiviral transgenic vector once, then the recognition scope of tumor antigens is expanded, but the efficiency in package of transgenic vector is low and gene transduction efficiency is very low
Solution Approach 1:
The patent divides the dual-CAR system into separate lentiviral vectors, with each vector carrying one CAR construct. This segmentation allows each vector to be optimized for its specific CAR, ensuring high packaging efficiency and transduction effectiveness for each antigen target independently.
Solution Approach 2:
The patent uses a universal lentiviral vector backbone that can accommodate different CAR constructs. This multi-functional platform allows the same vector system to deliver either single CAR or dual CAR configurations, maintaining high efficiency across different therapeutic applications.
2Adaptability or versatility
If two groups of CARs are transduced into primary T lymphocytes by transducing two lentiviral transgenic vectors twice, then the recognition scope of tumor antigens is expanded, but the time of transduction is long and primary cells are easy to age
Solution Approach 1:
The patent combines two separate transduction procedures into a single simultaneous transduction event by using a dual-CAR lentiviral vector system. This merging approach delivers both CAR constructs in one step, significantly reducing transduction time and minimizing exposure of primary T cells to stress conditions that cause aging.
3Adaptability or versatility
If a chimeric antigen receptor is designed to recognize two kinds of antigens, then the ability to eliminate diverse tumor cells is improved, but the volume of lentiviral transgenic vector is occupied and not good for loading other functional components
Solution Approach 1:
The patent segments the multiple antigen recognition functions into separate modular CAR units, each carried by its own lentiviral vector. This segmentation prevents any single vector from becoming overloaded, maintaining adequate capacity for essential vector components while distributing the antigen recognition load across multiple vectors.
Solution Approach 2:
The patent introduces a dual-CAR lentiviral vector system as an intermediary platform that facilitates the delivery of multiple CAR constructs. This intermediary system manages the complexity of multi-antigen recognition by organizing it into a structured, multi-component delivery platform that preserves vector capacity for essential functions.
Data Source
Figure 1~2B
Figure 3(A)~3(E)
Figure 4A~5D
AI summary
The invention discloses an OCTS-based CAR-T vector for treating spongioblastoma, consisting of lentiviral skeleton plasmid, human EF1α promoter (SEQ ID NO.14), OCTS chimeric receptor structural domain, and PDL1 single-chain antibody; the OCTS chimeric receptor structural domain consists of CD8 leader chimeric receptor signal peptide (SEQ ID NO.15), PDL1 single-chain antibody light chain VL (SEQ ID NO.16), PDL1 single-chain antibody heavy chain VH (SEQ ID NO.17), EGFRvIII single-chain antibody light chain VL (SEQ ID NO.18), EGFRvIII single-chain antibody heavy chain VH (SEQ ID NO.19), antibody Inner-Linker (SEQ ID NO.20), single-chain antibody Inter-Linker (SEQ ID NO.21), CD8 Hinge chimeric receptor linker (SEQ ID NO.22), CD8 Transmembrane chimeric receptor transmembrane domain (SEQ ID NO.23), TCR chimeric receptor T cell activation domain (SEQ ID N0.26) and chimeric receptor co-stimulator domain. Also, the invention discloses the preparation method and application in the preparation of drugs for treating spongioblastoma of the vector.