CD8b-Binding Polypeptides for Non-Invasive T-Cell Imaging
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Solution Overview
Problem
Current immunomodulating agents, particularly immune checkpoint inhibitors, are ineffective in a significant fraction of cancer patients, and existing non-invasive methods for monitoring therapeutic response to these agents lack spatial information and are not comprehensive, making it difficult to predict or follow up on treatment outcomes.
Innovation Solution
Development of polypeptides specifically binding to CD8b, comprising defined CDR and FR regions, which are humanized and can be labeled for use as immunotracers to provide non-invasive immune-monitoring imaging, allowing for in vivo visualization of T-cell rich organs and high tumor uptake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If invasive methods such as biopsies or blood biomarkers are used for therapy prediction, then some therapeutic information can be obtained, but complete overview of tumor micro-environment and spatial information are not provided
Solution Approach 1:
The patent uses CD8b-binding polypeptides as intermediary agents that can penetrate tissue and bind specifically to CD8b-expressing cells in the tumor microenvironment. These polypeptides serve as mediators between the imaging system and the target cells, enabling non-invasive detection of spatial distribution and therapeutic response without requiring invasive biopsies
Solution Approach 2:
The patent replaces mechanical invasive procedures (biopsies) with molecular imaging using CD8b-binding polypeptides. This substitution allows visualization of tumor microenvironment and cellular distribution through non-invasive imaging techniques, eliminating the need for physical tissue sampling while providing comprehensive spatial information
2Measurement precision
If non-invasive immune-monitoring imaging is used, then spatial information and complete overview of tumor micro-environment are provided, but the methods lack sensitivity and specificity for detecting therapeutic response
Solution Approach 1:
The patent employs CD8b-binding polypeptides with highly specific local binding properties to CD8b-expressing cells. This localized specific binding enhances detection sensitivity by concentrating the imaging signal at the target site while maintaining non-invasive operation, allowing precise visualization of therapeutic response in the tumor microenvironment
Solution Approach 2:
The patent utilizes radiolabeled or fluorescently labeled CD8b-binding polypeptides that change their detectable parameters when bound to target cells. This parameter change (from undetectable or low-signal state to high-signal state) enhances measurement precision for detecting therapeutic response while maintaining non-invasive imaging capabilities
3Reliability
If CD8a-targeting tracers are used, then some T-cell detection is achieved, but specificity for cytotoxic T-cells is reduced compared to CD8b-targeting
Solution Approach 1:
The patent extracts and targets specifically the CD8b subunit, which is uniquely expressed on cytotoxic T-cells, rather than targeting CD8a which is expressed on multiple cell types including NK cells. This extraction of the specific CD8b target provides higher reliability for cytotoxic T-cell detection while the modular polypeptide design keeps development complexity manageable
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 CD8b-binding polypeptides offer selective targeting of cytotoxic T-cells, providing high tumor-to-blood ratios and enabling effective molecular imaging for monitoring therapeutic response with improved specificity and sensitivity.
Implementation Method 1
polypeptides binding to CD8b, wherein the amino acid sequence of such polypeptides is comprising a CDR1 region, a CDR2 region, and a CDR3 region
Data Source
AI summary
The invention relates to polypeptides, in particular polypeptides comprising an immunoglobulin domain, binding to human and cynomolgus CD8b protein and to applications of such polypeptides such as for use as diagnostic agent, for example as an immunotracer.