Anti-mesothelin scFv for Rapid PET Tumor Imaging
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Solution Overview
Problem
Current cancer diagnosis and treatment methods lack effective targeting and imaging agents for mesothelin-expressing tumors, with conventional antibodies being immunogenic and inefficient for repeated administration.
Innovation Solution
Development of a low-molecular-weight anti-mesothelin single-chain variable fragment (scFv) antibody and tumor imaging agent, labeled with 89Zr for PET imaging, which allows for rapid visualization of mesothelin-expressing tumors and can be modified for targeting with antitumor agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional full-length antibodies are used for tumor imaging, then high specificity and affinity for mesothelin can be achieved, but the molecular weight is large resulting in slow blood clearance and delayed tumor visualization
Solution Approach 1:
The patent segments the full-length antibody into a single-chain variable fragment (scFv) comprising only the variable regions of heavy and light chains connected by a linker. This segmentation reduces the molecular weight from ~150 kDa to ~27 kDa while retaining the antigen-binding specificity, thereby achieving fast blood clearance and rapid tumor visualization within 3 hours post-injection
2Stability of the object's composition
If conventional full-length antibodies are used, then stable binding to mesothelin is achieved, but blood clearance is slow requiring long imaging times
Solution Approach 1:
By segmenting the antibody into scFv format, the patent achieves rapid blood clearance (half-life reduced from days to hours) while maintaining stable binding to mesothelin through preserved complementarity-determining regions (CDRs) that ensure specific antigen recognition
Solution Approach 2:
The patent changes the molecular weight parameter from full-length antibody (~150 kDa) to scFv (~27 kDa), which fundamentally alters the pharmacokinetic profile including blood clearance rate and tumor accumulation time, enabling imaging within 3 hours
3Reliability
If immunogenic antibodies are used for repeated administration, then initial tumor targeting can be achieved, but immune response develops limiting subsequent dosing
Solution Approach 1:
The patent uses humanized or human scFv sequences instead of murine antibodies, changing the immunogenicity parameter to reduce host immune response while maintaining tumor targeting effectiveness, thereby enabling repeated administrations for monitoring treatment response
4Measurement precision
If traditional imaging methods are used, then general tumor detection is possible, but specific visualization of mesothelin-expressing tumors is insufficient
Solution Approach 1:
The patent creates a universal scFv platform that can be labeled with different radionuclides (e.g., 89Zr for PET, 111In for SPECT) or fluorescent dyes, making it applicable to multiple imaging modalities while maintaining specific targeting of mesothelin-expressing tumors across different cancer types
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-mesothelin scFv enables specific and rapid visualization of tumors expressing mesothelin using PET imaging, with safer cancer imaging due to the absence of β-ray emission from 89Zr and potential for improved targeting with antitumor agents.
Implementation Method 1
labeled with 89Zr for PET imaging
Implementation Method 2
specific visualization of tumors expressing mesothelin using PET imaging
Data Source
AI summary
This invention provides a DNA comprising any of the following (a) to (c): (a) a DNA comprising any of the base sequences of positions 16 to 831 of SEQ ID NO: 1, positions 16 to 822 of SEQ ID NO: 3, positions 16 to 825 of SEQ ID NO: 5, positions 16 to 819 of SEQ ID NO: 7, positions 16 to 834 of SEQ ID NO: 9, and positions 16 to 828 of SEQ ID NO: 11; (b) a DNA encoding a polypeptide comprising any of the amino acid sequences of positions 1 to 272 of SEQ ID NO: 2, positions 1 to 269 of SEQ ID NO: 4, positions 1 to 270 of SEQ ID NO: 6, positions 1 to 268 of SEQ ID NO: 8, positions 1 to 273 of SEQ ID NO: 10, and positions 1 to 271 of SEQ ID NO: 12; and (c) a complementary strand of the DNA (a) or (b).