{"doi":"10.1101/2025.02.15.638388","title":"Development of iPSC-Derived T Cells Targeting EGFR Neoantigens in Non-Small Cell Lung Cancer","abstract":"ABSTRACT A long-sought goal of cancer immunotherapy is to mass-produce T cells that specifically target tumor neoantigens. One decisive challenge is the identification of neoantigens derived from cancer driver genes. Here, we identify T cells that recognize the NSCLC-associated EGFR C797S mutation, which confers resistance to current inhibitors and is linked to poor prognosis. To overcome limitations in T cell availability, we reprogrammed EGFR C797S-specific T cells into induced pluripotent stem cells (iPSCs) and re-differentiated them into CD8 T cells. These iPSC-derived T cells specifically recognized the EGFR C797S mutation and effectively killed cancer cells expressing this mutation. Our findings underscore the potential of targeting driver mutation-derived neoantigens for immunotherapy and demonstrate that iPSC-derived T cells can mediate antitumor effects. Collectively, this approach combining neoantigen identification with T cell reprogramming may offer a promising strategy for targeting drug-resistant tumors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":562336,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":274574,"name":"Toshinobu Nishimura","orcid":"0000-0002-5425-1708","position":1,"is_corresponding":false},{"id":565116,"name":"Jonathan Villanueva","orcid":"0000-0002-1789-6822","position":2,"is_corresponding":false},{"id":651945,"name":"Laura Amaya","orcid":"0000-0002-8742-9111","position":3,"is_corresponding":false},{"id":274571,"name":"Jonas L. Fowler","orcid":"0000-0003-0766-4320","position":4,"is_corresponding":false},{"id":845563,"name":"Taichi Isobe","orcid":"0000-0001-5686-1940","position":5,"is_corresponding":false},{"id":492812,"name":"Yusuke Nakauchi","orcid":"0000-0002-6943-3811","position":6,"is_corresponding":false},{"id":807001,"name":"Brandon Saavedra","orcid":"0000-0003-4211-9993","position":7,"is_corresponding":false},{"id":847651,"name":"Haojun Xu","orcid":"0000-0001-9600-1945","position":8,"is_corresponding":false},{"id":1416104,"name":"Mahito Nakanishi","orcid":"0000-0002-7068-7587","position":9,"is_corresponding":false},{"id":29458,"name":"Adam C. Wilkinson","orcid":"0000-0001-7406-0151","position":10,"is_corresponding":false},{"id":274575,"name":"Kyle M. Loh","orcid":"0000-0002-8042-0149","position":11,"is_corresponding":false},{"id":4863,"name":"Joseph B. Shrager","orcid":"0000-0003-0859-0589","position":12,"is_corresponding":false},{"id":1043962,"name":"Hiromitsu Nakauchi","orcid":"0000-0002-8122-2566","position":13,"is_corresponding":false},{"id":1043960,"name":"Kouta Niizuma","orcid":"0000-0003-1183-1873","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:56:05.550545Z","pmid":null,"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":[]}