Anti-PD-1 Antibody CDR Optimization for High-Affinity Binding
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies fail to effectively block the interaction between PD-1 and its ligands, limiting the enhancement of tumor-killing activity of CD8+ cytotoxic T cells and immune surveillance, particularly in cancers and viral infections.
Innovation Solution
Development of anti-PD-1 antibodies or functional fragments with high affinity and specificity to block PD-1/PD-L1 interaction, activating tumor-specific T cells and promoting immune responses without cross-reactivity with other CD28 family members.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to block PD-1/PD-L1 interaction, then some immune response enhancement is achieved, but the blocking effectiveness is insufficient and tumor-killing activity is not adequately enhanced
Solution Approach 1:
The patent modifies the antibody structure by optimizing the CDR regions, particularly CDR3 of the heavy chain and CDR3 of the light chain, to achieve higher affinity binding to PD-1. This structural parameter change resolves the contradiction by enhancing both blocking effectiveness and tumor-killing activity simultaneously
Solution Approach 2:
The patent focuses on optimizing specific local regions of the antibody (the CDR loops) rather than the entire molecule. By improving the local binding interface quality through CDR optimization, the overall antibody performance in blocking PD-1/PD-L1 interaction and enhancing tumor-killing activity is significantly improved
2Productivity
If antibodies with high affinity to PD-1 are developed, then tumor-killing activity is enhanced, but specificity may be compromised and cross-reactivity with other CD28 family members may occur
Solution Approach 1:
The patent optimizes the CDR regions to create a highly specific binding interface that recognizes unique epitopes on PD-1. The optimized CDR3 sequences in particular are designed to distinguish PD-1 from other CD28 family members, achieving both high affinity and high specificity simultaneously
Solution Approach 2:
Instead of designing antibodies that bind to conserved regions of CD28 family members, the patent targets unique, non-conserved epitopes on PD-1. This inverted approach of targeting差异性 rather than similarity ensures high specificity while maintaining high affinity for tumor-killing activity enhancement
Data Source
AI summary
This invention provides antibodies or functional fragments thereof that bind to PD-1 with high affinity. The invention provides nucleic acid molecules encoding the antibodies or the fragments thereof according to the present invention, expression vectors and host cells for expressing the antibodies or the functional fragments thereof according to the present invention, as well as methods for producing the antibodies or the functional fragments thereof according to the present invention. The present invention also provides immunoconjugates and pharmaceutical compositions comprising the antibodies or the functional fragments thereof according to the present invention. The present invention additionally provides methods for treating a plurality of diseases (comprising cancers, infectious diseases and inflammatory diseases) by using the antibodies or the functional fragments thereof disclosed herein.