Authors' Affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Clin Cancer Res. 2013 Sep 15;19(18):4941-50. doi: 10.1158/1078-0432.CCR-13-1253. Epub 2013 Sep 10.
The success of immunotherapy for the treatment of metastatic cancer is contingent on the identification of appropriate target antigens. Potential targets must be expressed on tumors but show restricted expression on normal tissues. To maximize patient eligibility, ideal target antigens should be expressed on a high percentage of tumors within a histology and, potentially, in multiple different malignancies.
A Nanostring probeset was designed containing 97 genes, 72 of which are considered potential candidate genes for immunotherapy. Five established melanoma cell lines, 59 resected metastatic melanoma tumors, and 31 normal tissue samples were profiled and analyzed using Nanostring technology.
Of the 72 potential target genes, 33 were overexpressed in more than 20% of studied melanoma tumor samples. Twenty of those genes were identified as differentially expressed between normal tissues and tumor samples by ANOVA analysis. Analysis of normal tissue gene expression identified seven genes with limited normal tissue expression that warrant further consideration as potential immunotherapy target antigens: CSAG2, MAGEA3, MAGEC2, IL13RA2, PRAME, CSPG4, and SOX10. These genes were highly overexpressed on a large percentage of the studied tumor samples, with expression in a limited number of normal tissue samples at much lower levels.
The application of Nanostring RNA counting technology was used to directly quantitate the gene expression levels of multiple potential tumor antigens. Analysis of cell lines, 59 tumors, and normal tissues identified seven potential immunotherapy targets for the treatment of melanoma that could increase the number of patients potentially eligible for adoptive immunotherapy.
免疫疗法治疗转移性癌症的成功与否取决于适当的靶抗原的识别。潜在的靶标必须在肿瘤上表达，但在正常组织上表现出有限的表达。为了最大限度地提高患者的合格性，理想的靶标抗原应该在组织学上的高比例肿瘤上表达，并可能在多种不同的恶性肿瘤中表达。
设计了一个 Nanostring 探针集，其中包含 97 个基因，其中 72 个被认为是免疫治疗的潜在候选基因。使用 Nanostring 技术对 5 种已建立的黑色素瘤细胞系、59 个切除的转移性黑色素瘤肿瘤和 31 个正常组织样本进行了分析。
在 72 个潜在的靶基因中，有 33 个在超过 20%的研究性黑色素瘤肿瘤样本中过表达。通过方差分析，有 20 个基因被鉴定为正常组织和肿瘤样本之间差异表达。对正常组织基因表达的分析确定了 7 个正常组织表达有限的基因，值得进一步考虑作为潜在的免疫治疗靶抗原：CSAG2、MAGEA3、MAGEC2、IL13RA2、PRAME、CSPG4 和 SOX10。这些基因在很大比例的研究性肿瘤样本中高度过表达，而在数量有限的正常组织样本中表达水平较低。
应用 Nanostring RNA 计数技术直接定量分析了多个潜在肿瘤抗原的基因表达水平。对细胞系、59 个肿瘤和正常组织的分析确定了 7 个潜在的免疫治疗靶点，用于治疗黑色素瘤，可以增加潜在适合过继免疫治疗的患者数量。
