HLA-A0201-Binding Polypeptide for Targeted T Cell Activation
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Solution Overview
Problem
Current cancer therapies, including surgery, radiotherapy, and chemotherapy, have limitations such as high tumor metastasis recurrence and severe side effects on normal cells, while traditional immunotherapies face challenges in specificity and effectiveness, particularly in activating targeted T cell immunity against tumor-specific polypeptides.
Innovation Solution
A polypeptide with high affinity to HLA-A0201, specifically overexpressed in various cancers, is used to activate specific T cell immunity, enabling the development of diagnostic kits, medicaments, and vaccines that target tumors with improved safety and effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional cancer therapies (surgery, radiotherapy, chemotherapy) are used, then tumor cells can be removed or killed, but tumor metastasis recurrence rate increases and severe side effects occur on normal cells
Solution Approach 1:
The patent applies local quality by designing a polypeptide vaccine that targets specific tumor-associated antigens (such as GLRA2 gene mutation products) rather than treating all cancer cells uniformly. The vaccine induces T cell immunity specifically against the mutant polypeptide sequence, allowing selective destruction of tumor cells while sparing normal cells that express the wild-type protein. This localized targeting approach resolves the contradiction between effective anti-tumor treatment and reduction of side effects on normal tissues.
Solution Approach 2:
The patent uses an intermediary mechanism by employing dendritic cells as antigen-presenting cells that process and present the tumor-associated polypeptide to T cells. The dendritic cells act as mediators between the tumor antigen and the immune system, enabling specific T cell activation without direct contact between cytotoxic agents and normal cells. This intermediary approach allows targeted immune response while protecting normal cells from direct therapeutic damage.
2Reliability
If traditional immunotherapies are used, then anti-tumor immunity can be enhanced, but specificity and effectiveness in activating targeted T cell immunity is insufficient
Solution Approach 1:
The patent applies segmentation by focusing on a specific segment of the tumor protein - the mutant polypeptide sequence resulting from GLRA2 gene mutation - rather than using broad tumor antigens. By isolating and presenting this specific mutant sequence (e.g., TLAFLIFNI) to the immune system, the vaccine achieves high specificity for T cell targeting. The segmented approach allows precise identification and targeting of tumor-specific antigens, resolving the contradiction between enhancing anti-tumor immunity and achieving specific T cell targeting.
Solution Approach 2:
The patent utilizes parameter changes by modifying the antigen presentation parameters - specifically using HLA-A0201 positive dendritic cells and optimizing the polypeptide sequence for high-affinity binding to HLA-A0201. This parameter optimization ensures that the mutant polypeptide is efficiently presented to CD8+ T cells, enhancing both the effectiveness and specificity of the immune response. The parameter changes in antigen processing and presentation mechanisms directly improve T cell targeting precision.
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 induces specific T cell responses, enhancing tumor diagnosis and treatment by stimulating CTL cells and TIL cells, leading to targeted therapy with reduced side effects and improved prognosis for HLA-A0201 positive subjects.
Implementation Method 1
The polypeptide binds with high affinity to HLA-A0201, thus having the ability to activate specific T cell immunity
Data Source
AI summary
Provided are a polypeptide and nucleic acid for encoding the polypeptide, a nucleic-acid construct, an expression vector, and a host cell containing the nucleic acid, an antigen-presenting cell presenting the polypeptide on the surface of the cell, and immune effector cell thereof, a pharmaceutical composition containing the polypeptide, a vaccine containing the nucleic acid, the nucleic acid construct, the expression vector, the host cell, the antigen-presenting cell, and the immune effector cell, and an antibody recognizing the polypeptide. Also provided is a therapeutic method using the polypeptide, the nucleic acid, the pharmaceutical composition, the vaccine, and the antibody. Also provided are a diagnosis method and diagnosis apparatus for detecting the described polypeptide. Also provided is an application of the polypeptide in preparing a vaccine, a tumor diagnosis kit, or a pharmaceutical composition, and an application of the polypeptide or the nucleic acid as a test target in tumor diagnosis.