Fusion Polypeptide Scaffold for Lymph Node Targeting
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Solution Overview
Problem
Current cancer immunotherapy faces challenges in identifying and delivering highly specific tumor neoantigens efficiently to maximize T cell activation, leading to limited use of tumor neoantigens in cancer vaccines.
Innovation Solution
A composition comprising a fusion polypeptide encoded by a nucleic acid molecule, which includes antigen polypeptides and scaffold polypeptides, where the scaffold polypeptides are connected through linker sequences to enhance solubility, stability, and lymph node targeting, facilitating antigen presentation and T cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tumor neoantigens are used in cancer vaccines, then tumor-specific immunogenicity is improved, but technical difficulties in identification, selection, and production limit their practical application
Solution Approach 1:
The patent combines multiple neoantigen sequences into a single fusion polypeptide construct, merging the identification, selection, and production steps into one integrated molecular entity that can be manufactured as a unified product
Solution Approach 2:
The fusion polypeptide scaffold serves multiple functions simultaneously: it displays multiple neoantigens for broad immunogenicity, provides structural stability for ease of production, and enables efficient delivery to lymph nodes, thereby addressing multiple technical challenges with a single universal construct
2Reliability
If multiple antigen polypeptides are delivered to maximize T cell activation, then anti-tumor immunogenicity is improved, but delivery efficiency and lymph node accumulation are reduced
Solution Approach 1:
Multiple antigen polypeptides are merged into a single fusion polypeptide molecule, allowing simultaneous delivery of multiple antigens through one molecular unit, thereby improving delivery efficiency while maintaining comprehensive T cell activation
Solution Approach 2:
The patent transitions from delivering multiple separate antigen molecules to delivering a single multidimensional fusion polypeptide that contains multiple antigen sequences, changing the dimensional organization of antigen delivery to improve pharmacokinetic properties and lymph node accumulation
3Stability of the object's composition
If fusion polypeptides with scaffold polypeptides are used, then solubility and stability are improved, but molecular complexity increases
Solution Approach 1:
The scaffold polypeptide provides localized structural quality improvements at specific regions of the fusion polypeptide, enhancing solubility and stability where needed without requiring complex modifications throughout the entire molecular structure
Solution Approach 2:
The fusion polypeptide is constructed as a composite molecular material combining antigen polypeptide sequences with scaffold polypeptide sequences, creating a stable soluble construct through the synergistic properties of its composite components
Data Source
AI summary
Disclosed herein is a protein fusion technology that allows the combination of one or more cancer vaccine epitopes with scaffold domains. Also disclosed herein are polypeptide and polynucleic acid compositions encompassed by the protein fusion technology and the methods of using the same.