SiiE-Derived Polypeptide Targets Long-Lived Plasma Cells
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Solution Overview
Problem
Current therapies are inadequate for effectively treating diseases associated with pathogenic long-lived plasma cells and there is a need for improved vaccination strategies against nontyphoidal Salmonella (NTS) bacteria.
Innovation Solution
A polypeptide with a specific amino acid sequence, sharing high similarity with laminin β1, is used to reduce plasma cells in the bone marrow by disrupting their interaction with laminin β1, and a mutant NTS bacterium lacking the SiiE protein is used as a vaccine to induce a robust humoral immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to treat diseases associated with pathogenic long-lived plasma cells, then treatment is provided, but the therapies are inadequate and fail to effectively eliminate pathogenic plasma cells
Solution Approach 1:
The patent uses a polypeptide derived from Salmonella SiiE protein as an intermediary agent that specifically binds to pathogenic plasma cells and disrupts their interaction with the bone marrow microenvironment, leading to their elimination. This intermediary approach overcomes the inadequacy of current direct therapies.
Solution Approach 2:
The patent exploits the natural interaction between Salmonella SiiE protein and host plasma cells, converting a potentially harmful bacterial mechanism into a beneficial therapeutic tool. The SiiE-derived polypeptide harnesses this interaction to specifically target and eliminate pathogenic plasma cells.
2Object-generated harmful factors
If long-lived plasma cells are targeted for elimination, then pathogenic antibodies are reduced, but current therapies fail to sufficiently eliminate these refractory cells
Solution Approach 1:
The patent changes the therapeutic parameter from non-specific B-cell depletion to specific targeting of pathogenic plasma cells through the SiiE-derived polypeptide. This parameter change enables reliable elimination of pathogenic cells while preserving protective immunity.
Solution Approach 2:
The patent segments the immune system into protective plasma cells and pathogenic plasma cells, using the SiiE-derived polypeptide to selectively target only the pathogenic segment. This segmentation allows elimination of harmful cells while maintaining beneficial immune function.
3Stability of the object's composition
If B-cell depletion therapies are used, then humoral memory is maintained, but pathogenic long-lived plasma cells are not sufficiently eliminated
Solution Approach 1:
The patent applies local quality by making the therapy specific to pathogenic plasma cells through the SiiE-derived polypeptide, rather than uniform depletion of all B cells. This localized targeting preserves humoral memory while eliminating pathogenic cells.
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 polypeptide effectively reduces the number of plasma cells and circulating antibodies, making pathogenic plasma cells accessible to other treatments, while the mutant NTS vaccine generates a strong immune response against NTS, providing protection against infection.
Implementation Method 1
A polypeptide with a specific amino acid sequence, sharing high similarity with laminin β1, is used to reduce plasma cells in the bone marrow by disrupting their interaction with laminin β1
Implementation Method 2
a mutant NTS bacterium lacking the SiiE protein is used as a vaccine to induce a robust humoral immune response
Data Source
AI summary
An isolated polypeptide includes the amino acid sequence EEAEKAKEAAEKALNEAFE or an amino acid sequence with a sequence identity of least 70%, 80%, or 90% identity to that sequence. The polypeptide is no longer than 200 or 170 amino acids. A nucleic acid encodes the polypeptide, a gene therapy vector includes the nucleic acid and genetically modified cells express the polypeptide. The polypeptide, the nucleic acid, the gene therapy vector and/or the cell can be used for the treatment of a disease associated with pathogenic long-lived plasma cells.