{"doi":"10.1136/jitc-2021-004035","title":"Development of a TCR-like antibody and chimeric antigen receptor against NY-ESO-1/HLA-A2 for cancer immunotherapy","abstract":"BACKGROUND: The current therapeutic antibodies and chimeric antigen receptor (CAR) T cells are capable of recognizing surface antigens, but not of intracellular proteins, thus limiting the target coverage for drug development. To mimic the feature of T-cell receptor (TCR) that recognizes the complex of major histocompatibility class I and peptide on the cell surface derived from the processed intracellular antigen, we used NY-ESO-1, a cancer-testis antigen, to develop a TCR-like fully human IgG1 antibody and its derivative, CAR-T cells, for cancer immunotherapy. METHODS: ) was screened against HLA-A2/NY-ESO-1 (peptide 157-165) complex to obtain target-specific antibodies. The specificity and affinity of those antibodies were characterized by flow cytometry, ELISA, biolayer interferometry, and confocal imaging. The biological functions of CAR-T cells were evaluated against target tumor cells in vitro. In vivo antitumor activity was investigated in a triple-negative breast cancer (TNBC) model and primary melanoma tumor model in immunocompromised mice. RESULTS: in the context of human leukocyte antigen HLA-A*02:01 but not to non-A2 or NY-ESO-1 negative cells. The second-generation CAR-T cells engineered from 2D2 specifically recognized and eliminated A2+/NY-ESO-1+tumor cells in vitro, inhibited tumor growth, and prolonged the overall survival of mice in TNBC and primary melanoma tumor model in vivo. CONCLUSIONS: This study showed the specificity of the antibody identified from human scFv phage library and demonstrated the potential antitumor activity by TCR-like CAR-T cells both in vitro and in vivo, warranting further preclinical and clinical evaluation of the TCR-like antibody in patients. The generation of TCR-like antibody and its CAR-T cells provides the state-of-the-art platform and proof-of-concept validation to broaden the scope of target antigen recognition and sheds light on the development of novel therapeutics for cancer immunotherapy.","journal":"Journal for ImmunoTherapy of Cancer","year":2022,"id":239212,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":742149,"name":"Yixiang Xu","orcid":"0000-0001-5793-7783","position":1,"is_corresponding":false},{"id":244930,"name":"Wei Xiong","orcid":"0000-0002-8087-5047","position":2,"is_corresponding":false},{"id":631180,"name":"Bingnan Yin","orcid":null,"position":3,"is_corresponding":false},{"id":864549,"name":"Yuqian Huang","orcid":"0000-0001-9380-3141","position":4,"is_corresponding":false},{"id":629724,"name":"Junjun Chu","orcid":"0000-0002-4916-5506","position":5,"is_corresponding":false},{"id":560709,"name":"Changsheng Xing","orcid":"0000-0001-6582-9037","position":6,"is_corresponding":false},{"id":629728,"name":"Qian Chen","orcid":"0009-0006-2281-0719","position":7,"is_corresponding":false},{"id":324082,"name":"Yang Du","orcid":"0000-0002-5307-448X","position":8,"is_corresponding":false},{"id":629725,"name":"Tianhao Duan","orcid":"0000-0002-1737-6114","position":9,"is_corresponding":false},{"id":371174,"name":"Helen Y. Wang","orcid":"0000-0002-3112-2081","position":10,"is_corresponding":false},{"id":284582,"name":"Ningyan Zhang","orcid":"0000-0002-4348-2180","position":11,"is_corresponding":false},{"id":648029,"name":"John S. Yu","orcid":"0000-0003-1230-8494","position":12,"is_corresponding":false},{"id":105313,"name":"Zhiqiang An","orcid":"0000-0001-9309-2335","position":13,"is_corresponding":false},{"id":324087,"name":"Rong‐Fu Wang","orcid":"0000-0002-8834-2763","position":14,"is_corresponding":false},{"id":294280,"name":"Xin Liu","orcid":"0000-0001-7949-1436","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:22:36.865157Z","pmid":"35338087","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}