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Updated: Nov 9, 2025
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Identification of NY-ESO-1157-165 Specific Murine T Cell Receptors With Distinct Recognition Pattern for Tumor
Helin Zhang1,2, Meng Sun1,2, Jie Wang3,4
1Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
Abstract:
New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target for T-cell receptor-engineered T cell (TCR-T) therapy, and targeting the human leukocyte antigen (HLA)-A2 restricted NY-ESO-1157-165 epitope has yielded remarkable clinical benefits in the treatment of multiple advanced malignancies. Herein, we report the identification of two NY-ESO-1157-165 epitope-specific murine TCRs obtained from HLA-A*0201 transgenic mice. NY-ESO-1157-165 specific TCRs were isolated after vaccinating HLA-A2 transgenic mice with epitope peptides. HZ6 and HZ8 TCRs could specifically bind to NY-ESO-1157-165/HLA-A2 and were capable of cytokine secretion with engineered Jurkat T cells and primary T cells upon recognition with K562 target cells expressing the single-chain trimer (SCT) of NY-ESO-1157-165/HLA-A2. The reactivity profiles of the HZ6 and HZ8 TCRs were found to be distinct from one another when co-cultured with K562 target cells carrying alanine-substituted NY-ESO-1157-165 SCTs. The binding characterization revealed that the recognition pattern of the HZ6 TCR to NY-ESO-1157-165/HLA-A2 was substantially different from the widely used 1G4 TCR. These findings would broaden the understanding of immunogenicity of the NY-ESO-1157-165, and the two identified TCRs may serve as promising candidates for the future development of TCR-T therapy for tumors.
Insights
Two novel T-cell receptors (TCRs) targeting the NY-ESO-1157-165 epitope in HLA-A2 cancers were identified. These TCRs show promise for developing new T-cell receptor-engineered T cell (TCR-T) therapies for advanced malignancies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen is a validated target for T-cell receptor-engineered T cell (TCR-T) therapy.
- NY-ESO-1157-165 epitope presented by human leukocyte antigen (HLA)-A2 has demonstrated significant clinical efficacy in advanced cancers.
Purpose of the Study:
- To identify and characterize novel murine T-cell receptors (TCRs) specific for the NY-ESO-1157-165/HLA-A2 complex.
- To evaluate the functional activity and binding characteristics of these newly identified TCRs for potential TCR-T therapy development.
Main Methods:
- Isolation of NY-ESO-1157-165 epitope-specific TCRs from HLA-A*0201 transgenic mice immunized with epitope peptides.
- Assessment of TCR binding to NY-ESO-1157-165/HLA-A2 using engineered Jurkat and primary T cells.
- Evaluation of cytokine secretion and reactivity profiles using K562 target cells expressing NY-ESO-1157-165 single-chain trimers (SCTs), including alanine-substituted variants.
Main Results:
- Two NY-ESO-1157-165 epitope-specific murine TCRs, HZ6 and HZ8, were successfully identified.
- HZ6 and HZ8 TCRs demonstrated specific binding to NY-ESO-1157-165/HLA-A2 and induced cytokine secretion in engineered T cells.
- Distinct reactivity profiles were observed for HZ6 and HZ8 against alanine-substituted epitopes, and HZ6 showed a different recognition pattern compared to the established 1G4 TCR.
Conclusions:
- The identified HZ6 and HZ8 TCRs provide new tools for understanding NY-ESO-1157-165 immunogenicity.
- These TCRs represent promising candidates for the future development of advanced TCR-T therapies targeting NY-ESO-1-expressing tumors.
