PMID- 33833762 OWN - NLM STAT- MEDLINE DCOM- 20210923 LR - 20210923 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Identification of NY-ESO-1(157-165) Specific Murine T Cell Receptors With Distinct Recognition Pattern for Tumor Immunotherapy. PG - 644520 LID - 10.3389/fimmu.2021.644520 [doi] LID - 644520 AB - 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-1(157-165) epitope has yielded remarkable clinical benefits in the treatment of multiple advanced malignancies. Herein, we report the identification of two NY-ESO-1(157-165) epitope-specific murine TCRs obtained from HLA-A(*)0201 transgenic mice. NY-ESO-1(157-165) specific TCRs were isolated after vaccinating HLA-A2 transgenic mice with epitope peptides. HZ6 and HZ8 TCRs could specifically bind to NY-ESO-1(157-165)/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-1(157-165)/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-1(157-165) SCTs. The binding characterization revealed that the recognition pattern of the HZ6 TCR to NY-ESO-1(157-165)/HLA-A2 was substantially different from the widely used 1G4 TCR. These findings would broaden the understanding of immunogenicity of the NY-ESO-1(157-165), and the two identified TCRs may serve as promising candidates for the future development of TCR-T therapy for tumors. CI - Copyright (c) 2021 Zhang, Sun, Wang, Zeng, Cao, Han, Tan and Gao. FAU - Zhang, Helin AU - Zhang H AD - Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China. AD - University of Chinese Academy of Sciences, Beijing, China. FAU - Sun, Meng AU - Sun M AD - Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China. AD - University of Chinese Academy of Sciences, Beijing, China. FAU - Wang, Jie AU - Wang J AD - Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. AD - College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang, China. FAU - Zeng, Bin AU - Zeng B AD - College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang, China. AD - College of Pharmacy, Shenzhen Technology University, Shenzhen, China. FAU - Cao, Xiaoqing AU - Cao X AD - Beijing Chest Hospital, Capital Medical University, Beijing, China. FAU - Han, Yi AU - Han Y AD - Beijing Chest Hospital, Capital Medical University, Beijing, China. FAU - Tan, Shuguang AU - Tan S AD - University of Chinese Academy of Sciences, Beijing, China. AD - Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. FAU - Gao, George F AU - Gao GF AD - Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China. AD - University of Chinese Academy of Sciences, Beijing, China. AD - Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210323 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (Neoplasm Proteins) RN - 0 (Peptide Fragments) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (peptide NY-ESO-1 157-165) SB - IM MH - Animals MH - HEK293 Cells MH - HLA-A2 Antigen/genetics/*metabolism MH - Humans MH - *Immunotherapy MH - Jurkat Cells MH - K562 Cells MH - Mice MH - Mice, Transgenic MH - Neoplasm Proteins/*immunology MH - Neoplasms/genetics/immunology/*therapy MH - Peptide Fragments/*immunology MH - Receptors, Antigen, T-Cell/genetics/*immunology MH - T-Lymphocytes/*immunology PMC - PMC8021954 OTO - NOTNLM OT - New York esophageal squamous cell carcinoma 1 OT - T cell receptor-engineered-T cell OT - T-cell receptor OT - human leukocyte antigen-A*0201 OT - tumor COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/04/10 06:00 MHDA- 2021/09/24 06:00 PMCR- 2021/01/01 CRDT- 2021/04/09 06:26 PHST- 2020/12/21 00:00 [received] PHST- 2021/02/15 00:00 [accepted] PHST- 2021/04/09 06:26 [entrez] PHST- 2021/04/10 06:00 [pubmed] PHST- 2021/09/24 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.644520 [doi] PST - epublish SO - Front Immunol. 2021 Mar 23;12:644520. doi: 10.3389/fimmu.2021.644520. eCollection 2021.