PBF-Derived Peptide for HLA-A2 Binding and CTL Induction
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Solution Overview
Problem
Current cancer immunotherapies lack a tumor antigen peptide that binds to HLA-A2 antigen, limiting their effectiveness in inducing cytotoxic T cells for treating sarcomas and renal cancers.
Innovation Solution
Identification and utilization of a fragment peptide from the papillomavirus binding factor (PBF) protein, specifically designed to bind to HLA-A2 antigen, which serves as a tumor antigen peptide for inducing cytotoxic T cells and acting as a tumor marker.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional tumor antigen proteins are used for cancer immunotherapy, then existing tumor-specific CTLs can be induced, but no effective peptide can be obtained that binds to HLA-A2 antigen
Solution Approach 1:
The PBF protein is divided into multiple peptide segments, and each segment is screened for its ability to bind to HLA-A2 antigen. This segmentation approach allows identification of specific epitopes (peptide sequences) within the larger protein that have the desired binding property, resolving the contradiction between using conventional tumor antigens and achieving HLA-A2 binding capability.
Solution Approach 2:
The amino acid sequence parameters of the tumor antigen are modified by identifying and isolating specific peptide sequences from the PBF protein that have optimal binding affinity to HLA-A2. This parameter change transforms the conventional tumor antigen approach into a targeted peptide-based therapy with proven HLA-A2 binding capability.
2Ease of operation
If tumor antigen peptides are identified for specific HLA types, then CTL induction is possible, but peptides binding to HLA-A2 have not been found
Solution Approach 1:
The specific peptide sequences binding to HLA-A2 are extracted and isolated from the complete PBF protein sequence. This extraction process identifies the precise amino acid segments (epitopes) that can bind to HLA-A2 and induce CTLs, solving the problem of unavailable HLA-A2 binding peptides while maintaining CTL induction capability.
3Reliability
If PBF protein is used as tumor antigen, then it shows activity against sarcomas and renal cancers, but lacks identified peptides for HLA-A2 presentation
Solution Approach 1:
The peptide sequences from PBF that can bind to HLA-A2 are identified and characterized in advance through systematic screening. This preliminary identification of epitopes preserves the anti-tumor activity of PBF while providing the specific peptide sequence information needed for HLA-A2 presentation, eliminating the information loss.
Data Source
AI summary
Disclosed is a peptide consisting of the identical amino acid sequence or a substantially identical amino acid sequence to the amino acid sequence depicted in SEQ ID NO:4, wherein the peptide binds to an HLA antigen and is recognized by cytotoxic T cells. The peptide of the present invention can be used in vivo or in vitro as an agent for inducing CTL, that is, cancer vaccine, and exerts therapeutic or ameliorating effects on tumors such as osteosarcoma, renal cancer, and others. The peptide of the present invention is also useful as a tumor marker directed to tumors such as sarcoma, renal cancer, and others.