Ayyoub Maha, Brehm Michelle, Metthez Geneviève, Talbot Susan, Dutoit Valerie, Taub Robert N, Keohan Mary-Louise, Gure Ali O, Chen Yao-Tseng, Williamson Barbara, Jungbluth Achim A, Old Lloyd J, Hesdorffer Charles S, Valmori Danila
Ludwig Institute Clinical Trial Center, Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Cancer Immun. 2003 Oct 9;3:13.
The efficacy of current standard therapies for the treatment of sarcoma remains limited. With the aim of identifying target antigens relevant to the development of vaccine-based immunotherapy of sarcoma, we have addressed the relevance of tumor-specific antigens encoded by genes belonging to the SSX family as vaccine targets in sarcoma tumors. Expression of SSX-1 to -5 was analyzed in a collection of sarcoma tumors of diverse histological subtypes and in sarcoma cell lines. We found expression of at least one SSX-encoded antigen in 42% of sarcoma tumors, including 5 of 7 different histological subtypes, and in 50% of sarcoma cell lines. SSX-1 was the most frequently expressed family member, followed by SSX-4, -2 and -5. Expression of SSX-3 was detected in only one sample. Importantly, most SSX positive samples co-expressed more than one family member. In addition, assessment of CD8+ T cell recognition of HLA-A2+ SSX-2+ sarcoma cells showed that the latter were efficiently recognized and lysed by SSX-2-specific CTLs. The results of this study indicate that SSX antigens are relevant targets for the development of vaccine-based immunotherapy of sarcoma and encourage the start of vaccination trials using SSX-derived immunogens in sarcoma patients.
目前用于治疗肉瘤的标准疗法疗效仍然有限。为了确定与基于疫苗的肉瘤免疫疗法发展相关的靶抗原，我们研究了属于SSX家族的基因所编码的肿瘤特异性抗原作为肉瘤肿瘤疫苗靶点的相关性。在一系列不同组织学亚型的肉瘤肿瘤和肉瘤细胞系中分析了SSX-1至-5的表达。我们发现在42%的肉瘤肿瘤中至少有一种SSX编码抗原表达，包括7种不同组织学亚型中的5种，在50%的肉瘤细胞系中也有表达。SSX-1是最常表达的家族成员，其次是SSX-4、-2和-5。仅在一个样本中检测到SSX-3的表达。重要的是，大多数SSX阳性样本共表达不止一个家族成员。此外，对HLA-A2+ SSX-2+肉瘤细胞的CD8+ T细胞识别评估表明，后者被SSX-2特异性CTL有效识别并裂解。这项研究的结果表明，SSX抗原是基于疫苗的肉瘤免疫疗法发展的相关靶点，并鼓励在肉瘤患者中开始使用SSX衍生免疫原进行疫苗试验。
