Antigen Short Peptide Screening for HLA-A1101 TCRs
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Solution Overview
Problem
Current T cell immunotherapy methods for HPV-related diseases, such as cervical cancer, are limited by the tumor microenvironment's immunosuppression and the polymorphic nature of MHC molecules, making it difficult to identify effective antigenic short peptides that can be presented by HPV-expressing tumor cells and recognized by TCRs.
Innovation Solution
The use of antigenic short peptides, represented by SEQ ID NO: 1 or SEQ ID NO: 2, to screen for T cell receptors (TCRs) that specifically bind to the HLA-A1101 complex, enabling T cells to be activated and effectively target HPV-positive tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional T cell immunotherapy methods are used for HPV-related diseases, then treatment can be provided, but the tumor microenvironment's immunosuppression limits effectiveness
Solution Approach 1:
The patent identifies specific antigenic short peptides (SEQ ID NO: 1 and SEQ ID NO: 2) that change the parameters of T cell recognition by matching them to HLA-A1101 molecular structures, thereby overcoming the immunosuppressive environment through precise molecular parameter optimization
Solution Approach 2:
The antigenic short peptides serve as intermediaries that bridge the gap between T cells and HPV-positive tumor cells, enabling specific recognition and activation despite the immunosuppressive tumor microenvironment
2Measurement precision
If TCR screening is performed without specific antigenic peptides, then general T cell activity can be maintained, but it is difficult to identify effective antigenic short peptides that can be presented by HPV-expressing tumor cells
Solution Approach 1:
The patent performs preliminary identification and characterization of specific antigenic short peptides (SEQ ID NO: 1 and SEQ ID NO: 2) that are naturally presented by HPV-expressing tumor cells, making subsequent TCR screening more efficient and precise
Solution Approach 2:
The identified antigenic short peptides have universal applicability for screening TCRs that can recognize HPV-positive tumor cells across different patients, especially those with HLA-A1101 expression
3Adaptability or versatility
If MHC polymorphism is considered in TCR therapy design, then broader population coverage can be achieved, but the complexity of identifying matching peptides increases
Solution Approach 1:
The patent focuses on the specific local quality of HLA-A1101 molecular structure and its corresponding antigenic short peptides, providing a targeted solution that balances population coverage with screening feasibility
Data Source
AI summary
Disclosed in the present application are the use of an antigen short peptide in screening a drug for treating HPV-related diseases and a TCR screened by same, wherein the amino acid sequence of the antigen short peptide is as shown in SEQ ID NO: 1 or SEQ ID NO: 2. In the present application, the antigen short peptide can be used to screen a specific T cell receptor (TCR), and the T cell transduced with the TCR can be specifically activated and have a very strong killing effect on tumor cells expressing A1101 and HPV, which can be used for immunotherapy of HPV positive tumors, such as cervical cancer. In addition, the T cell transduced with the TCR of the present application has a strong activation reaction on a cell line expressing E6, has no activation reaction on a cell line not expressing E6, and has a very strong killing function on the cell line expressing E6 and can effectively inhibit the growth of E6 positive tumors.