Fu Chenghao, Bian Chengyu, Zhu Weiyou, Du Haonan, Han Linrui, Zhu Jian, Wang Jun, Cao Lei
Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Front Immunol. 2025 Sep 1;16:1637165. doi: 10.3389/fimmu.2025.1637165. eCollection 2025.
Adoptive cell therapy (ACT), an important component of tumor immunotherapy, achieves precise anti-cancer effects by reinfusing -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.
过继性细胞疗法（ACT）是肿瘤免疫疗法的重要组成部分，通过回输经过处理的免疫细胞实现精准抗癌效果，为对化疗或靶向治疗耐药的晚期肿瘤患者提供了新的选择。其中，抗原特异性细胞毒性T淋巴细胞（ACTL）疗法创新性地整合了肿瘤浸润淋巴细胞（TILs）的自然扩增优势和重组腺相关病毒转染树突状细胞（rAAV-DCs）的精准抗原呈递机制，成为研究热点。本病例报告描述了一名IVa期晚期肺腺癌伴多发肺内转移的患者，携带表皮生长因子受体（EGFR）外显子19缺失突变。在接受第三代EGFR酪氨酸激酶抑制剂（EGFR-TKI）药物奥希替尼治疗后，患者出现了机制不明的获得性耐药，并处于免疫抑制状态。随后，该患者接受了ACTL治疗，最终实现了临床完全缓解（cCR），并在六年的随访中保持这一状态。该病例首次报道ACTL疗法在获得性EGFR-TKI耐药患者中实现了“临床治愈”，间接提示了该疗法重塑肿瘤免疫微环境（TME）的潜在机制。它表明，ACTL作为一种兼具靶向精准性和免疫平衡性的新型细胞免疫疗法，在克服晚期肺癌靶向耐药和诱导深度缓解方面显示出了潜力。
