Antisense Oligonucleotides for B7-H4 Targeting
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Solution Overview
Problem
Current methods for blocking B7-H4 activity in cancer treatment are limited by low stability, enzyme degradation, innate immune activation, and lack of specific targeting, making antisense nucleic acids ineffective for clinical use.
Innovation Solution
Development of isolated polynucleotides encoding human anti-B7-H4 antibodies or fragments, specifically designed to inhibit B7-H4-dependent T cell inhibition, including methods for diagnosing and treating B7-H4-related diseases by administering these antibodies or genetically modified cells with chimeric antigen receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antisense nucleic acids are used to block B7-H4 activity, then B7-H4 expression can be reduced, but the treatment suffers from low stability, enzyme degradation, and innate immune activation
Solution Approach 1:
The patent uses antisense nucleic acids that complementarily bind to B7-H4 mRNA to inhibit protein synthesis, creating a molecular copy-based blocking mechanism that avoids direct protein-protein interference while achieving reliable B7-H4 activity blockade without the stability issues of protein-based agents
Solution Approach 2:
The patent modifies the chemical parameters of the nucleic acid blocking agents through various modifications (such as phosphorothioate backbones, 2'-O-methyl modifications) to enhance stability against enzyme degradation while maintaining complementary binding to B7-H4 mRNA, thereby resolving the stability contradiction
2Object-affected harmful factors
If antisense nucleic acids are administered for B7-H4 blocking, then T cell inhibition can be reduced, but the treatment lacks specific targeting and causes innate immune activation
Solution Approach 1:
The patent employs antisense nucleic acids as intermediary molecules that specifically bind to B7-H4 mRNA through complementary base pairing, acting as a mediator between the therapeutic agent and the target gene without directly interacting with proteins, thereby achieving specific T cell activation without off-target immune activation
Solution Approach 2:
The patent replaces mechanical or protein-based blocking mechanisms with a molecular recognition system based on nucleic acid complementary binding, where the antisense oligonucleotide specifically recognizes and binds to B7-H4 mRNA sequence, providing high specificity without the limitations of protein-based approaches
3Productivity
If B7-H4 activity is blocked to enhance anti-tumor immunity, then tumor growth can be inhibited, but current methods have low clinical effectiveness
Solution Approach 1:
The patent uses antisense nucleic acids to preliminarily block B7-H4 mRNA translation before tumor progression occurs, preventing the immunosuppressive effect from establishing, thereby enhancing anti-tumor immunity more effectively than approaches that attempt to reverse established suppression
Solution Approach 2:
The patent employs modified nucleic acid copies (antisense oligonucleotides) that specifically target and inhibit B7-H4 mRNA, providing a more reliable and effective mechanism for blocking B7-H4 activity compared to protein-based inhibitors, thereby improving clinical effectiveness in enhancing anti-tumor immune responses
Data Source
AI summary
The present invention relates to B7-H4-specific compositions and methods of use thereof.