{"title":"评估乳腺癌中 MAGE-A4 的表达及其对预后的影响。","authors":"Kaho Nakamura, Kanako Saito, Chihiro Higashi, Yuji Kozuka, Hiroto Yuasa, Yurina Nishimura, Makoto Ishitobi, Mikiya Ishihara, Toshiro Mizuno, Isao Tawara, Taizo Shiraishi, Tomoko Ogawa, Shinichi Kageyama, Yoshihiro Miyahara","doi":"10.1111/cas.16433","DOIUrl":null,"url":null,"abstract":"<p><p>Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of MAGE-A4 expression in breast cancer and its impact on prognosis.\",\"authors\":\"Kaho Nakamura, Kanako Saito, Chihiro Higashi, Yuji Kozuka, Hiroto Yuasa, Yurina Nishimura, Makoto Ishitobi, Mikiya Ishihara, Toshiro Mizuno, Isao Tawara, Taizo Shiraishi, Tomoko Ogawa, Shinichi Kageyama, Yoshihiro Miyahara\",\"doi\":\"10.1111/cas.16433\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.</p>\",\"PeriodicalId\":48943,\"journal\":{\"name\":\"Cancer Science\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cas.16433\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cas.16433","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
黑色素瘤相关抗原(MAGE)-A4是一种睾丸癌抗原，是嵌合抗原受体T细胞治疗难治性实体瘤（包括乳腺癌）的一个有希望的靶点。然而，缺乏针对MAGE-A4的高特异性抗体是MAGE-A4靶向免疫疗法发展的主要挑战。本研究旨在验证一种新型MAGE-A4 Ab （E701U）的特异性，并检测MAGE-A4在临床BC样本中的表达。将MAGE-A1、-A2B、-A3、-A4、-A6、-A9、-A10和-A12基因转染HEK293细胞。使用E701U抗体评估每个插入细胞块中MAGE-A4的表达。随后，我们使用E701U免疫组化方法评估了403例原发性BC组织样本中MAGE-A4的表达，并分析了MAGE-A4在早期BC患者中的临床影响。结果表明，MAGE-A4的表达仅限于转染MAGE-A4基因的细胞。5.7%的BC样本中有MAGE-A4表达。三阴性BC的阳性率明显高于其他亚型。MAGE-A4(+) BC患者的5年总生存率明显低于MAGE-A4(-) BC患者。此外，MAGE-A4(+) BC患者的5年无复发生存率（RFS）明显低于MAGE-A4(-) BC患者。MAGE-A4表达是RFS的独立预后因素。综上所述，E701U Ab对MAGE家族基因中MAGE- a4的表达具有可靠的特异性。MAGE-A4(+) BC患者预后不良，是MAGE-A4特异性免疫治疗的潜在候选者。
Evaluation of MAGE-A4 expression in breast cancer and its impact on prognosis.
Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.
期刊介绍：
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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