CD38/CD138 Hybrid Antibody-Peptide for ACPA Plasma Cell Targeting
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Solution Overview
Problem
Current treatments for rheumatoid arthritis focus on managing flare-ups and preventing their occurrence, with no cure available, and existing methods do not effectively target and eliminate the source of anti-citrullinated protein autoantibodies (ACPA) produced by plasma cells.
Innovation Solution
A hybrid molecule comprising a fibrin-derived peptide with citrullyl residues covalently linked to an antibody or antibody fragment that binds to CD38 and/or CD138, allowing specific targeting and elimination of ACPA-secreting plasma cells through apoptosis, phagocytosis, ADCC, or complement activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional fibrin peptides are used for immune response modulation, then they can activate immune cells, but they also promote unwanted blood clot formation and have short half-life
Solution Approach 1:
The hybrid molecule is designed as a segmented structure with distinct functional domains: an N-terminal domain containing the fibrin-derived citrullinated peptide sequence (RQPIR) for immune cell activation, and a C-terminal domain containing the antibody fragment for binding to CD38/CD138. This segmentation allows each domain to perform its specific function independently while being part of a unified molecule, thereby achieving reliable immune response modulation without the harmful effects of conventional fibrin peptides.
Solution Approach 2:
The invention creates a composite molecular structure by combining two different biologically active components: a citrullinated fibrin peptide epitope and an antibody fragment (such as single-chain Fv or nanobody). This composite hybrid molecule integrates the immune-stimulating properties of the fibrin peptide with the targeting and stabilizing properties of the antibody fragment, thereby achieving reliable immune modulation while eliminating the unwanted blood clot formation and extending half-life.
2Reliability
If fibrin peptides are used to activate immune cells, then immune response is enhanced, but the peptides are rapidly degraded and have limited circulation time
Solution Approach 1:
The invention merges the fibrin-derived citrullinated peptide sequence with an antibody fragment into a single hybrid molecule. The antibody fragment portion provides structural stability and protection against proteolytic degradation, thereby extending the circulation half-life of the molecule while preserving the immune cell activation capability provided by the citrullinated peptide epitope.
3Adaptability or versatility
If conventional peptides are used for targeted therapy, then they can reach specific cells, but they lack specificity and bind to multiple cell types
Solution Approach 1:
The hybrid molecule exhibits local quality differentiation: the N-terminal citrullinated peptide domain provides broad immune cell recognition, while the C-terminal antibody fragment domain provides highly specific targeting to CD38 or CD138 antigens on specific cell types such as plasma cells. This local differentiation of binding properties within different parts of the molecule enables precise targeting while maintaining versatility.
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 hybrid molecule effectively eliminates ACPA-secreting plasma cells, reducing the source of autoantibodies and inducing remission of rheumatoid arthritis by targeting plasma cells using CD38 and CD138 markers and recognizing ACPAs, thereby addressing the underlying cause of the disease.
Implementation Method 1
Hybrid molecule comprising a fibrin-derived citrullinated peptide and an antibody or antibody fragment which binds to cd38 and/or cd138
Implementation Method 2
an antibody or antibody fragment which binds to cd38 and/or cd138
Data Source
Figure 1A~1B
Figure 2~3
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AI summary
The invention relates to a hybrid molecule comprising a fibrin-derived citrullinated peptide and an antibody or antibody fragment which binds to CD38 and/or CD138, to the uses of such a hybrid molecule, and also to the method for producing same.