Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Cancer. 2012 Sep 15;118(18):4564-70. doi: 10.1002/cncr.27446. Epub 2012 Feb 22.
Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors.
The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay.
A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated.
The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL.
黏液样/圆细胞脂肪肉瘤(MRCL)是第二常见的脂肪肉瘤亚型,占脂肪肉瘤的>33%,约占所有软组织肉瘤的 10%。尽管 MRCL 是一种化疗敏感的亚型,但转移性疾病患者的预后较差。NY-ESO-1 是一种癌症睾丸抗原(也称为癌症生殖细胞抗原),已成功在疫苗试验和过继性 T 细胞治疗试验中针对几种实体瘤进行靶向治疗。
作者通过使用免疫组织化学和定量逆转录聚合酶链反应分析评估肿瘤中 NY-ESO-1 的表达,来研究针对 MRCL 患者靶向 NY-ESO-1 的可行性。还使用铬释放测定分析了 NY-ESO-1 特异性 T 细胞对 NY-ESO-1 特异性肿瘤的识别。
对华盛顿大学肉瘤组织库的搜索确定了 25 名 MRCL 患者的石蜡包埋肿瘤样本。评估的每例 MRCL 肿瘤均观察到 NY-ESO-1 表达(100%);在 18 例肿瘤(72%)中,染色均匀。除了 2 例肿瘤外,其余肿瘤的染色均足够强(2+),这些患者有资格参加 NY-ESO-1 定向治疗的临床试验。通过使用 NY-ESO-1 特异性、CD8 阳性 T 细胞,证明了黏液样脂肪肉瘤细胞系对抗原特异性溶解的体外敏感性。
目前的结果确立了 NY-ESO-1 作为治疗 MRCL 患者的重要靶抗原。