Anti-LILRB2 Antibodies for Blocking Tumor Immune Suppression
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Solution Overview
Problem
There is a need for more effective immunotherapy treatments targeting LILRB2, a potent inhibitory molecule overexpressed in tumor microenvironments, which suppresses immune responses and correlates with poor patient outcomes in cancers like NSCLC and breast cancer.
Innovation Solution
Development of novel antibodies or antigen-binding fragments that specifically bind to LILRB2, blocking its interactions with HLA-A2, HLA-G, ANGPTL1, ANGPTL2, ANGPTL4, ANGPTL7, and MAG, and reprogramming M2 macrophages to a pro-inflammatory M1 phenotype, enhancing immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If LILRB2 is overexpressed in tumor microenvironment, then immune suppression increases and correlates with poor patient outcomes, but conventional immunotherapy effectiveness decreases
Solution Approach 1:
The patent extracts and neutralizes the harmful LILRB2 molecule from the tumor microenvironment by administering anti-LILRB2 antibodies that specifically bind to and block LILRB2's immune suppressive functions, thereby removing the obstacle to effective immunotherapy
Solution Approach 2:
The patent converts the harmful immune suppressive effect of LILRB2 into a beneficial therapeutic outcome by using anti-LILRB2 antibodies to block LILRB2's inhibitory function, thereby transforming the tumor's immune evasion mechanism into an opportunity for enhanced immune activation and anti-tumor immunity
2Reliability
If LILRB2 blocks interactions with HLA molecules and other ligands, then immune response is suppressed, but developing antibodies that block all these interactions simultaneously increases molecular complexity
Solution Approach 1:
The patent creates universal anti-LILRB2 antibodies that can simultaneously block multiple LILRB2 interactions with different ligands (HLA-A2, HLA-G, ANGPTL1, ANGPTL2, ANGPTL4, ANGPTL7, and MAG), allowing a single antibody structure to perform multiple blocking functions
Solution Approach 2:
The patent segments the complex interaction network by specifically targeting and blocking LILRB2's interactions with individual ligand families (MHC class I molecules, ANGPTL family, MAG) through engineered antibody binding sites, thereby simplifying the overall immune activation process
Data Source
AI summary
The present disclosure relates to an antibody or antigen-binding fragment thereof that binds to LILRB2 (Leukocyte Immunoglobulin Like Receptor B2), the anti-LILRB2 antibody or antigen-binding fragment thereof could block the signaling pathway and upregulates the immune response to a LILRB2-related disease, disorder, or condition.