Anti-PD-1 Antibody CDR Tuning for Stronger Checkpoint Blockade
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Solution Overview
Problem
Existing immune checkpoint inhibitors targeting PD-1 face challenges with unresponsive patients and autoimmune side effects, necessitating new inhibitors to enhance cancer immunotherapy efficacy and address primary immunodeficiencies and infectious diseases.
Innovation Solution
Development of anti-PD-1 antibodies and antigen-binding fragments with specific CDR sequences, including humanized antibodies, that bind to PD-1 with high affinity and inhibit the PD-1/PD-L1 interaction, stimulating T cell activation and cytokine secretion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing PD-1 targeted therapy is used, then cancer treatment efficacy is improved, but unresponsive patients and autoimmune side effects occur
Solution Approach 1:
The patent applies parameter changes by developing novel antibody variants with modified CDR sequences and affinity characteristics. Specifically, the invention creates anti-PD-1 antibodies with tuned binding affinities through amino acid substitutions in the complementarity-determining regions, thereby optimizing therapeutic efficacy while potentially reducing off-target autoimmune effects.
Solution Approach 2:
The patent employs local quality by making specific amino acid substitutions in particular regions of the antibody structure (CDR1, CDR2, CDR3 of both heavy and light chains). These localized modifications alter the interaction interface with PD-1, enabling fine-tuned control over binding characteristics and therapeutic profile without affecting the entire antibody molecule.
2Reliability
If PD-1 inhibition is enhanced to treat unresponsive patients, then cancer immunotherapy efficacy is improved, but autoimmune response risks increase
Solution Approach 1:
The patent utilizes parameter changes by systematically varying amino acid residues in the antibody CDR regions to modulate binding affinity and specificity. This allows optimization of the therapeutic window, enhancing efficacy for unresponsive patients while minimizing autoimmune side effects through precise affinity tuning.
Solution Approach 2:
The patent employs copying by creating multiple antibody variants based on a parent anti-PD-1 antibody structure. These variants replicate the core therapeutic function while incorporating specific mutations to improve efficacy and safety profiles, effectively copying and optimizing the parental molecule's beneficial properties.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibodies effectively treat various cancers, infectious diseases, and primary immunodeficiencies by enhancing immune response and reducing PD-1/PD-L1 interaction, demonstrating potent in vitro and in vivo efficacy.
Implementation Method 1
anti-PD-1 antibodies and antigen-binding fragments with specific CDR sequences, including humanized antibodies, that bind to PD-1 with high affinity and inhibit the PD-1/PD-L1 interaction
Implementation Method 2
stimulating T cell activation and cytokine secretion
Data Source
AI summary
The present disclosure relates to antibodies and anti-gen-binding fragments that bind specifically to the human programmed cell death protein 1 (PD-1) and methods for treating cancer or other diseases with said antibodies and antigen-binding fragments.