{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T16:17:37Z","timestamp":1768925857665,"version":"3.49.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Adoptive cell therapy (ACT), an important component of tumor immunotherapy, achieves precise anti-cancer effects by reinfusing <jats:italic>in vitro<\/jats:italic>-processed immune cells, providing a new option for advanced tumor patients with resistance to chemotherapy or targeted therapy. Among them, antigen-specific cytotoxic T lymphocyte (ACTL) therapy innovatively integrates the natural expansion advantage of tumor-infiltrating lymphocytes (TILs) and the precise antigen-presenting mechanism of recombinant adeno-associated virus-transfected dendritic cells (rAAV-DCs), becoming a research focus. This case report describes a patient with IVa stage advanced lung adenocarcinoma with multiple intrapulmonary metastases carrying an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. After receiving treatment with the third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) drug osimertinib, the patient developed acquired resistance with unknown mechanisms and was in an immune-suppressed state. Subsequently, the patient received ACTL therapy and ultimately achieved a clinical complete response (cCR) and maintained it for six years of follow-up. This case is the first to report that ACTL therapy has achieved \u201cclinical cure\u201d in a patient with acquired EGFR-TKI resistance, indirectly suggesting the underlying mechanism of this therapy in reshaping the tumor immune microenvironment (TME). It illustrates that ACTL, as a novel cellular immunotherapy with both target precision and immune balance, has demonstrated potential in overcoming targeted resistance in advanced lung cancer and inducing deep remission.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1637165","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T05:31:30Z","timestamp":1756704690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Durable complete response to antigen-specific cytotoxic T lymphocyte therapy in advanced EGFR-TKI resistant lung adenocarcinoma: a case of adoptive cellular immunotherapy overcoming acquired targeted resistance"],"prefix":"10.3389","volume":"16","author":[{"given":"Chenghao","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengyu","family":"Bian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyou","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haonan","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linrui","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","unstructured":"Global 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