Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
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DOI：
10.1200/jco.2010.32.2537
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发表时间：
2011-03-01
影响因子：
45.3
通讯作者：
Rosenberg, Steven A.
中科院分区：
文献类型：
--
作者：
Robbins, Paul F.;Morgan, Richard A.;Rosenberg, Steven A.
目的利用肿瘤浸润性淋巴细胞进行免疫治疗是治疗转移性黑色素瘤的有效方法。NY-ESO-1癌症/睾丸抗原在80%的滑膜细胞肉瘤患者和约25%的黑色素瘤和常见上皮肿瘤患者中表达，代表了基于免疫的治疗的有吸引力的靶点。目前的试验进行了评估的能力，过继转移自体T细胞转导的T细胞受体（TCR）直接对NY-ESO-1介导的转移性黑色素瘤和滑膜细胞sarcoma.Patients和方法转移性黑色素瘤或转移性滑膜细胞肉瘤难治性的所有标准治疗的患者中的肿瘤消退。NY-ESO-1阳性肿瘤患者用自体TCR转导的T细胞加720，000 iU/kg白细胞介素-2治疗，以在准备化疗后耐受。结果NY-ESO-1表达的6例滑膜细胞肉瘤患者中有4例和11例黑色素瘤患者中有5例观察到客观临床反应。11例黑色素瘤患者中有2例在1年后完全消退。持续18个月的部分反应，观察1例滑膜细胞sarcoma.Conclusion这些观察表明，TCR为基础的基因治疗针对NY-ESO-1黑色素瘤和滑膜细胞肉瘤患者代表了一种新的和有效的治疗方法。据我们所知，这是首次证明使用TCR转导的T细胞成功治疗非黑色素瘤肿瘤。
Purpose Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma.Patients and Methods A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1-positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).Results Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma.Conclusion These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.