CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1637165
This article is part of the Research TopicBreaking Barriers: New Frontiers in Immunotherapy for Resistant CancersView all 4 articles
Durable complete response to antigen-specific cytotoxic T lymphocyte (ACTL) therapy in advanced EGFR-TKI resistant lung adenocarcinoma: a case of adoptive cellular immunotherapy overcoming acquired targeted resistance
Provisionally accepted
- 1First Affiliated Hospital, Nanjing Medical University, Nanjing, China
- 2Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China
- 3The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- 4People's Liberation Army General Hospital of Central Theater Command, Wuhan, China
- 5Suqian First Hospital, Suqian, China
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Adoptive cell therapy (ACT), an important component of tumor immunotherapy, achieves precise anti-cancer effects by reinfusing in vitro-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 "clinical cure" 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.
Keywords: ACTL, EGFR-TKI, Resistance, Advanced NSCLC, cellular immunotherapy
Received: 28 May 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Fu, Chengyu, Zhu, 杜, Han, Zhu, Wang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chenghao Fu, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
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