Anti-CD150 Nanobody Blocking for Reversing T Cell Exhaustion
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Solution Overview
Problem
Conventional monoclonal antibodies for treating malignant tumors have large molecular weights, complex production processes, and limited amenability to engineering, leading to severe side effects and secondary drug resistance, while CD150 is a target for measles virus-mediated oncolysis and contributes to T cell exhaustion in tumor progression.
Innovation Solution
Development of an anti-CD150 nanobody with high binding activity that blocks the interaction between CD150 and its ligand, reversing T cell exhaustion and enhancing tumor cell killing, utilizing alpaca-derived single-domain antibodies with specific CDR sequences and humanization to improve specificity and reduce immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional monoclonal antibodies are used for treating malignant tumors, then therapeutic efficacy can be achieved, but severe side effects and secondary drug resistance occur
Solution Approach 1:
The patent divides the conventional monoclonal antibody into a single-domain nanobody fragment, retaining only the essential variable region (VHH) while removing the constant regions and glycosylation sites. This segmentation reduces molecular weight and eliminates glycosylation-dependent functions, thereby reducing immunogenicity and side effects while maintaining anti-CD150 binding activity and therapeutic efficacy.
Solution Approach 2:
The patent changes the molecular parameters of the antibody by removing glycosylation sites and reducing the number of amino acid residues. The nanobody has a molecular weight of approximately 15 kDa compared to 150 kDa for conventional antibodies, and lacks glycosylation modifications. This parameter change reduces immunogenicity and improves pharmacokinetic properties, leading to reduced side effects and lower resistance to drug efficacy.
2Reliability
If conventional monoclonal antibodies are used, then tumor treatment can be achieved, but the production process becomes complex and engineering modification is limited
Solution Approach 1:
The patent extracts only the essential functional element (the variable region VHH) from the complete monoclonal antibody structure. By taking out the constant regions, hinge regions, and glycosylation sites, the production process is simplified to express only the nanobody fragment, which can be produced in bacterial systems without complex eukaryotic post-translational modifications, thereby reducing production complexity.
Solution Approach 2:
The patent segments the antibody molecule into a minimal functional unit (nanobody) that can be independently expressed and purified. This segmentation allows for simplified production processes using prokaryotic expression systems, avoiding the complex eukaryotic cell culture and purification steps required for conventional monoclonal antibodies, while maintaining tumor treatment efficacy through CD150 targeting.
3Reliability
If conventional monoclonal antibodies are used, then anti-tumor activity can be achieved, but the molecules have large molecular weight and limited penetration
Solution Approach 1:
The patent extracts and removes the heavy constant regions and glycosylation structures from the conventional antibody, retaining only the minimal variable region (VHH) necessary for CD150 binding. This extraction reduces the molecular weight from approximately 150 kDa to 15 kDa, enabling better penetration into tumor tissues and improved pharmacokinetic properties while maintaining anti-tumor activity through specific antigen targeting.
Solution Approach 2:
The patent fundamentally changes the molecular weight parameter by designing a nanobody with only 110-150 amino acid residues compared to 400-500 residues in conventional antibodies. This parameter change reduces the molecule size, improving diffusion coefficients and penetration capabilities into solid tumors, while the retained variable region maintains high-affinity binding to CD150 for anti-tumor efficacy.
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 anti-CD150 nanobody effectively kills tumor cells by blocking CD150 interactions, avoiding secondary drug resistance and improving treatment efficacy with reduced immunogenicity.
Implementation Method 1
The anti-CD150 nanobody effectively kills tumor cells by blocking CD150 interactions
Implementation Method 2
The nanobody reverses the functional exhaustion of T cells, B cells, and NK cells by blocking the interaction between CD150 and its ligand
Data Source
AI summary
Provided is a nanobody or antigen-binding fragment capable of specifically recognizing CD150. The antibody or antigen-binding fragment comprises heavy chain variable region CDR sequences selected from at least one of following sequences: SEQ ID NO: 1 to SEQ ID NO: 3, or amino acid sequences having at least 80% identity with same. The antibody has low immunogenicity, and can specifically target and bind CD150. By means of blocking the function of CD150 and a ligand thereof, the antibody can reverse the function depletion of immune cells, thereby achieving the effect of killing tumor cells.