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Updated: Sep 13, 2025
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Author Spotlight: Exploring Strategies for Successful Immune Response Against Tumors
Published on: August 16, 2024
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Integrated system for screening tumor-specific TCRs, epitopes, and HLA subtypes using single-cell sequencing data
Xianyao Wang1,2, Xuelian Song1, Yi Li1,3
1National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China.
Journal for Immunotherapy of Cancer
|July 31, 2025
Summary
Researchers developed a rapid TCR assembly and screening system to identify tumor-specific T-cell receptors (TCRs) for cancer immunotherapy. This method successfully isolated a human papillomavirus (HPV)-specific TCR, demonstrating its potential for advancing TCR-T cell therapies.
Area of Science:
- Immunotherapy
- Oncology
- Molecular Biology
Background:
- T-cell receptor (TCR)-T immunotherapy shows promise for cancer treatment.
- Identifying tumor-specific TCRs is challenging due to tumor heterogeneity, T cell scarcity, and HLA diversity.
- Efficient and scalable methods are needed to discover TCRs for TCR-T cell generation.
Purpose of the Study:
- To develop a rapid and cost-effective method for assembling and screening tumor-specific TCRs.
- To engineer antigen-presenting cells for personalized HLA-I and neoantigen expression.
- To validate a TCR screening system using human papillomavirus (HPV)-specific TCRs.
Main Methods:
- Developed a method for rapid TCR assembly using synthesized oligonucleotides for CDR3 regions.
- Engineered HLA-knockout HEK-293T cells to express patient-specific HLA-I and neoantigens.
- Utilized a Jurkat NFAT-GFP reporter cell line for screening antigen-reactive TCRs.
Main Results:
- Successfully constructed TCR libraries within 2 days, accelerating the process and reducing costs.
- Demonstrated flexible expression of patient-specific HLA-I molecules for personalized screening.
- Isolated a functional HPV-specific TCR recognizing an HPV-E7 peptide presented by HLA-B*15:18, which effectively killed HPV-positive cells.
Conclusions:
- Developed an integrated system for TCR assembly, antigen presentation, and reporter-based screening.
- Successfully identified a functional HPV-specific TCR, validating the system's efficacy.
- The approach holds significant potential for efficient screening of tumor-specific TCRs to advance TCR-T immunotherapy.
