CD24-Binding CAR Proteins with Short Variable-Region Linkers
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Solution Overview
Problem
Existing chimeric antigen receptors (CARs) exhibit low activity, weak cytotoxic efficacy, and safety concerns in vivo, necessitating optimization for enhanced antitumor activity and improved safety.
Innovation Solution
Development of an antigen-binding protein, such as a chimeric antigen receptor (CAR), with specific modifications including a linker length of 10 amino acids or less between light and heavy chain variable regions, and incorporation of chemokine receptors like CXCR2 and cytokines like IL-12β, to enhance cell activation, cytokine secretion, and antitumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing CAR structures are used, then the basic antitumor function is achieved, but the cytotoxic efficacy is weak and activity is low
Solution Approach 1:
The patent optimizes the linker length between light and heavy chain variable regions to 10 amino acids or less, and adjusts the structure of costimulatory domains to enhance cell activation ability and cytotoxic efficacy while maintaining antitumor activity
Solution Approach 2:
The patent incorporates multiple functional elements including chemokine receptors (CXCR2) and cytokines (IL-12β) into the CAR structure to create a composite receptor that simultaneously enhances activation, persistence, and cytotoxic efficacy
2Reliability
If CAR structures are optimized for higher activity, then antitumor efficacy is improved, but cytokine secretion increases causing safety concerns
Solution Approach 1:
The patent fine-tunes the linker length and costimulatory domain structure to achieve optimal balance between antitumor efficacy and cytokine secretion, reducing excessive cytokine release while maintaining killing ability
Solution Approach 2:
The patent designs CAR structures that provide regulated feedback control of cytokine secretion, allowing sustained antitumor activity while preventing harmful cytokine storms through optimized signal transduction pathways
3Productivity
If the linker length is reduced to 10 amino acids or less, then cell activation ability is enhanced, but structural flexibility may be reduced
Solution Approach 1:
The patent identifies 10 amino acids or less as the optimal linker length parameter that maximizes cell activation ability while maintaining sufficient structural flexibility through careful selection of amino acid composition and sequence
Data Source
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AI summary
Provided are a group CD24 binding proteins and uses thereof. Specifically provided is a group of antigen binding proteins, wherein cells expressing the antigen binding protein can have cytotoxicity and safety. Also provided is a use of the antigen binding protein in the preparation of a medication.