PD-L1 Nanobody for Cancer Treatment via Segmentation
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Solution Overview
Problem
Current monoclonal antibodies against PD-L1 are limited by large molecular weight, high immunogenicity, long development cycles, high production costs, and instability, which hinders their effectiveness in cancer treatment due to poor penetration and low affinity.
Innovation Solution
Development of specific nanobodies with optimized complementary determining regions (CDRs) and frame regions (FRs) of the VHH chain, which are more stable, immunogenicity, and have strong penetration and targeting capabilities, overcoming the limitations of traditional antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional monoclonal antibodies are used against PD-L1, then they can bind to PD-L1, but their large molecular weight (150 kD) prevents effective tissue penetration, resulting in lower effective concentration in tumor region
Solution Approach 1:
The patent segments the conventional monoclonal antibody into a nanobody format, retaining only the essential variable region (VHH) that binds to PD-L1 while removing the heavy and light chains. This segmentation reduces the molecular weight from 150 kD to approximately 15 kD, enabling effective tissue penetration while maintaining binding capability to PD-L1.
2Reliability
If traditional monoclonal antibodies are used, then they can target PD-L1, but they exhibit high immunogenicity and require complex humanization processes
Solution Approach 1:
The patent extracts the antigen-binding function from the conventional antibody structure, isolating the variable region (VHH) that provides PD-L1 binding capability. By removing the immunogenic constant regions and using a simplified nanobody format with optimized CDRs, the invention maintains targeting capability while significantly reducing immunogenicity.
3Reliability
If conventional monoclonal antibodies are developed, then they can achieve therapeutic effect, but the development cycle is long and production costs are high
Solution Approach 1:
The patent changes the fundamental parameters of the antibody structure by adopting a nanobody format with optimized CDR sequences. This structural parameter change enables faster development cycles and simplified production processes while maintaining therapeutic effectiveness against PD-L1.
4Reliability
If conventional monoclonal antibodies are used, then they can inhibit PD-1/PD-L1 interaction, but they show poor stability and require stringent storage conditions
Solution Approach 1:
The patent optimizes the nanobody structure with stabilized CDR sequences and framework regions that provide enhanced conformational stability. This dynamic structural optimization allows the nanobody to maintain its inhibitory function against PD-1/PD-L1 interaction while exhibiting improved stability and reduced storage requirements compared to conventional monoclonal antibodies.
Data Source
AI summary
Disclosed is a nanobody against the human programmed death factor PD-LI. The antibody has the function of blocking the binding of PD-LI to the receptor PD-I. Disclosed are the nanobody and the gene sequence encoding the nanobody, the corresponding expression vector and the host cell capable of expressing the nanobody, and the method for producing the nanobody. At the same time, also disclosed is the sequence of the humanized PD-LI nanobody. The humanized nanobody still has the function of blocking the binding of PD-LI to PD-1, and has a relatively high affinity and a relatively good specificity.