PD-1 Single Domain Antibody Multivalent Constructs
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Solution Overview
Problem
Current therapeutic molecules targeting PD-1 are inadequate in effectively modulating immune responses to treat diseases like cancer.
Innovation Solution
Development of binding polypeptides, including multivalent and multispecific constructs, that specifically bind to PD-1, thereby blocking its interaction with PD-L1 and PD-L2, and modulating immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic molecules targeting PD-1 are used, then immune responses are modulated, but the effectiveness in treating cancer is inadequate
Solution Approach 1:
The patent segments the antibody structure into single-domain units (VHH or VH) that can be independently configured. These modular domains are then assembled into multivalent constructs with specific arrangements (e.g., (VHH)2, (VHH)3, (VHH)4 configurations) to achieve enhanced PD-1 blocking activity while maintaining controllable complexity through systematic domain组合
Solution Approach 2:
The patent creates composite therapeutic molecules by combining multiple antibody domains with different functions into single constructs. These composite molecules include PD-1 binding domains paired with various Fc regions or other functional domains, achieving synergistic effects that improve cancer treatment effectiveness beyond what single-domain antibodies can provide
2Manufacturing precision
If multivalent and multisspecific constructs are developed, then binding specificity to PD-1 is improved, but molecular complexity increases
Solution Approach 1:
The patent uses segmented single-domain antibody units as standardized building blocks. Each VHH or VH domain is independently characterized and validated for PD-1 binding, then systematically assembled into multivalent constructs using defined linkers and configurations, ensuring consistent binding specificity while managing complexity through modular design
Solution Approach 2:
The patent creates universal PD-1 binding domains that can be paired with various Fc regions or functional modules to generate multiple multispecific constructs. The same PD-1 binding domain can be combined with different effector domains to achieve diverse therapeutic functions (e.g., ADC, bispecific antibodies), reducing the need to develop entirely new specific binding domains for each application
Data Source
AI summary
Provided herein are binding polypeptides that specifically bind PD-1. More specifically, provided herein are fusion proteins, including multivalent and/or multispecific constructs and chimeric antigen receptors, that bind PD-1. Also provided are pharmaceutical compositions containing the polypeptides, nucleic acid molecules encoding the polypeptides and vectors and cells thereof, and methods of use and uses of the provided PD-1 binding polypeptides for treating diseases and conditions, such as cancer.