Adair Sara J, Carr Tiffany M, Fink Mitsú J, Slingluff Craig L, Hogan Kevin T
Department of Surgery and the Human Immune Therapy Center, University of Virginia, Charlottesville, VA 22908, USA.
J Immunother. 2008 Jan;31(1):7-17. doi: 10.1097/CJI.0b013e318159f797.
The TAG-1, TAG-2a, TAG-2b, and TAG-2c cancer/testis genes, known to be expressed in an unusually high percentage of melanoma cell lines, are shown here to be expressed in a variety of tumor lines of diverse histologic type, including cancers of the brain, breast, colon, lung, ovary, pharynx, and tongue. The genes are also expressed in fresh, uncultured melanoma, and ovarian cancer cells. Epitope prediction algorithms were used to identify potential HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 epitopes, and these potential epitopes were tested for their ability to stimulate a peptide-specific cytotoxic T lymphocyte response using lymphocytes from healthy donors. Two HLA-A2-restricted epitopes (SLGWLFLLL and LLLRLECNV) were identified using this approach. Cytotoxic T lymphocytes specific for each of these peptides were capable of recognizing tumor cells expressing both the corresponding class I major histocompatibility complex encoded molecule and the TAG genes. These results indicate that TAG-derived peptides may be good components of a therapeutic vaccine designed to target melanoma and a variety of epithelial cell-derived malignancies.
已知TAG-1、TAG-2a、TAG-2b和TAG-2c癌/睾丸基因在异常高比例的黑色素瘤细胞系中表达，本文显示它们在多种不同组织学类型的肿瘤细胞系中表达，包括脑癌、乳腺癌、结肠癌、肺癌、卵巢癌、咽癌和舌癌。这些基因也在新鲜的、未培养的黑色素瘤和卵巢癌细胞中表达。使用表位预测算法鉴定潜在的HLA-A1、HLA-A2、HLA-A3、HLA-B7和HLA-B8表位，并使用健康供体的淋巴细胞测试这些潜在表位刺激肽特异性细胞毒性T淋巴细胞反应的能力。通过这种方法鉴定出两个HLA-A2限制性表位（SLGWLFLLL和LLLRLECNV）。对这些肽各自具有特异性的细胞毒性T淋巴细胞能够识别表达相应I类主要组织相容性复合体编码分子和TAG基因的肿瘤细胞。这些结果表明，源自TAG的肽可能是设计用于靶向黑色素瘤和多种上皮细胞源性恶性肿瘤的治疗性疫苗的良好组成部分。
