← 返回前沿论文

病例报告:抗原特异性细胞毒性 T 淋巴细胞治疗晚期 EGFR-TKI 耐药肺腺癌获得持久完全缓解:一例过继性细胞免疫治疗克服获得性靶向耐药的病例

英文原题: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.

PubMed 2025/09/01(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

过继性细胞治疗(ACT)是肿瘤免疫治疗的重要组成部分,通过回输体外处理过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。

中文摘要

过继性细胞治疗(ACT)是肿瘤免疫治疗的重要组成部分,通过回输体外处理后的免疫细胞实现精准抗癌效果,为化疗或靶向治疗耐药的晚期肿瘤患者提供了新选择。其中,抗原特异性细胞毒性T淋巴细胞(ACTL)治疗创新性地整合了TIL(肿瘤浸润淋巴细胞)的自然扩增优势和重组腺相关病毒转染树突状细胞(rAAV-DC)的精准抗原呈递机制,成为研究热点。本病例报告描述了一例携带表皮生长因子受体(EGFR)外显子19缺失突变的IVa期晚期肺腺癌伴多发肺内转移患者。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,患者出现机制不明的获得性耐药,并处于免疫抑制状态。随后,患者接受ACTL治疗,最终获得临床完全缓解(cCR),并在六年随访中维持该状态。本病例首次报道ACTL治疗在获得性EGFR-TKI耐药患者中实现“临床治愈”,间接提示该疗法重塑肿瘤免疫微环境(TME)的潜在机制。它表明ACTL作为一种兼具靶点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展现出潜力。

展开英文摘要原文

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.

论文信息

作者
Fu C、Bian C、Zhu W、Du H、Han L、Zhu J、Wang J、Cao L
第一作者单位
Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.China
通讯作者单位
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.China
文献类型
病例报告
期刊
Frontiers in immunology2025
原文标识
PubMed 40959071 · DOI 10.3389/fimmu.2025.1637165