更新于：2024-11-01

MAGEA10

更新于：2024-11-01

基本信息

别名

Cancer/testis antigen 1.10、cancer/testis antigen family 1, member 10、CT1.10

+ [7]

简介

Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.

关联

项与 MAGEA10 相关的药物

MAGE-A10 (Anocca)

靶点

MAGEA10

作用机制

MAGEA10抑制剂

在研机构

Anocca AB初创企业

原研机构

Anocca AB初创企业

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

Anti-MAGEA10 TCR-T therapy(Corregene Biotechnology)

靶点

MAGEA10

作用机制

MAGEA10抑制剂

在研机构-

原研机构

北京可瑞生物科技有限公司

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

Melanoma-associated antigen A10-specific T-cells (Adaptimmune)

靶点

MAGEA10

作用机制

MAGEA10抑制剂 [+2]

在研机构-

原研机构

Adaptimmune Ltd.

在研适应症-

非在研适应症

恶性上皮肿瘤 [+4]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 MAGEA10 相关的临床试验

NCT03391791 / TerminatedN/A

Long Term Follow-up of Subjects Exposed to Genetically Engineered Tumor Antigen Specific T Cell Receptors

Subjects who previously took part in an Adaptimmune study and received genetically changed T cells (including but not limited to MAGE-A10ᶜ⁷⁹⁶T and MAGE-A4ᶜ¹º³²T) are asked to take part in this long term follow-up study. Subjects will be asked to join this study once they complete the parent interventional study.
The purpose of this study is to find out if the genetically changed T cells that subjects received in the parent study have any long-term side effects. No additional study drug will be given, but subjects can receive other therapies for their cancer while they are being followed for long term safety in this study.
For a period of 15 years starting from last administration of the genetically changed T cells, subjects will visit their study doctor for a check-up and to have blood tests to look for any changes that might have happened because of the genetically changed T cells.

开始日期2018-02-28

申办/合作机构

Adaptimmune Ltd.

NCT02989064 / Completed临床1期

Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors

This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose.
The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer.
Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.

开始日期2016-10-01

申办/合作机构

Adaptimmune Ltd.

NCT02592577 / Completed临床1期

A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)

This first time in human study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A*02:01 and/or HLA-A*02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.
When the MAGE A10ᶜ⁷⁹⁶T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.
Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years. Subjects who have a confirmed response or clinical benefit ≥4 weeks after the first T-cell infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the Interventional Phase of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.

开始日期2015-11-01

申办/合作机构

Adaptimmune Ltd.

100 项与 MAGEA10 相关的临床结果

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100 项与 MAGEA10 相关的转化医学

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0 项与 MAGEA10 相关的专利（医药）

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项与 MAGEA10 相关的文献（医药）

2024-05-01·European Journal of Cancer

Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ

Article

作者: Bonanni, Bernardo ; Fumagalli, Caterina ; Taormina, Sergio Vincenzo ; Cammarata, Giulio ; Guerini-Rocco, Elena ; Viale, Giuseppe ; Cannone, Maria ; Concardi, Alberto ; Lazzeroni, Matteo ; Bellerba, Federica ; Guerrieri-Gonzaga, Aliana ; Balladore, Emanuela ; Del Fiol Manna, Eliza ; Fusco, Nicola ; Barberis, Massimo ; Gandini, Sara ; Veronesi, Paolo ; Macis, Debora

BACKGROUND AND AIMDuctal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with highly variable clinical behavior, but risk stratification is still challenging. We sought to identify immune-related gene expression signatures of pure DCIS associated with different risks of breast cancer recurrence.METHODSA retrospective nested case-control study of 143 pure DCIS was performed including 70 women with subsequent ipsilateral breast event (IBE, in situ or invasive; cases) and 73 DCIS women with no IBE and matched for age, tumor size, treatment, hormone receptors/HER2 status, and follow-up time (controls). RNA was extracted from DCIS samples and subjected to next-generation sequencing gene expression analysis of 395 immune-related genes. Correlations between DCIS immune-related gene expression and IBE were analyzed using weighted Cox regression for nested case-control data.RESULTSEight immune-related genes were differentially expressed between cases and controls. MAGEA10 expression (present vs. absent) and high expression levels of IFNA17 and CBLB (Q4 vs. Q1) were observed more frequently in DCIS of women with subsequent IBE, mainly invasive (p-value_FDR < 0.05). Conversely, expression of IL3RA1, TAGAP, TNFAIP8, and high expression levels of CCL2 and LRP1 were associated with a lower risk of IBE (p-value_FDR < 0.05).CONCLUSIONThis exploratory analysis of pure DCIS showed significant differences in immune-related gene expression profiles between women with and with no subsequent IBE, particularly as invasive IBE. These results, after additional validation, could improve risk stratification and management of DCIS patients.

2023-12-01·International Immunopharmacology

Diagnostic performance of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma

Article

作者: Wang, Peng ; Ye, Hua ; Wang, Keyan ; Shi, Jianxiang ; Zhang, Xiaoyue ; Li, Jiaxin ; Xia, Junfen ; Sun, Guiying ; Li, Tiandong ; Cheng, Yifan ; Chen, Huili

MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.

2023-07-01·Asian Pacific journal of cancer prevention : APJCP

The MAGE A1-A10 Expression associated with Histopathological Findings of Malignant or Non-Malignant Cells in Peripheral Lung Tumors.

Article

作者: Atika, - ; Rahaju, Anny Setijo ; Rahniayu, Alphania ; Amin, Mochamad ; Mastutik, Gondo ; Marhana, Isnin Anang ; Trianto, Heru Fajar ; Kurniassari, Nila

OBJECTIVEThe objective was to evaluate the expression of melanoma antigen (MAGE) A from A1 to 10 (A1-10) and the individual MAGE A family in the peripheral lung tumors and to analyze its association with histopathological findings.METHODSA cross-sectional study was conducted on 67 samples of peripheral lung tumor obtained by core biopsies from patients with clinical diagnoses such as lung and mediastinal tumors. The specimens were divided into two, one to perform histopathological diagnosis and the last for mRNA MAGE A examination. A Nested polymerase chain reaction (PCR) was performed using universal primer, MF10/MR10 and MF10/MR12. The collected data were analyzed by appropriate statistical techniques.RESULTThe histopathological finding showed 41 (61.2 %) of specimens as malignant cells and 26 (38.8 %) of specimens as non-malignant cells. MAGE A1-10 was expressed at 47 (70.1 %) and MAGE A1-6 was expressed at 25 (37.3 %) of specimens. In a malignant cell, MAGE A1-10 and MAGE A1-6 were expressed at 33 (80.5 %) and 19 (46.3 %), respectively. In non-malignant cells, MAGE A1-10 and MAGE A1-6 were expressed at 14 (53.9 %) and 6 (23.1 %,) respectively. The MAGE A1-10 and MAGE A8 expressions were significantly associated with histopathological findings of malignant or non-malignant cells. The sensitivity, specificity, and diagnostic accuracy of MAGE A1-10 were 80.5 %, 46.2 %, and 67.2 %, respectively; while for MAGE A8 were 41.5 %, 88.5 %, and 59.7 %, respectively.CONCLUSIONThe MAGE A1-10 expression was the most commonly detected and associated with the histopathological finding. Moreover, it was more sensitive and specific and had higher diagnostic accuracy than others. Therefore, the MAGE A1-10 assay may improve the accuracy of the diagnosis of malignancy in peripheral lung tumors.

项与 MAGEA10 相关的新闻（医药）

2022-06-03

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测胎龄、防早产、先兆子痫，比尔盖茨看中的Mirvie获FDA突破性设备认证

人类的遗传物质主要存在于细胞内，但血液中也漂浮着少量的DNA和RNA，通常是由垂死的细胞释放。在孕妇中，这种物质来自胎儿、胎盘和母亲。生物技术公司Mirvie通过使用机器学习和液体活检技术，开发出一种适用于孕妇的迅速、简单、个性化血液测试。该测试将用于在孕期发现并预防妊娠病发症，如早产、先兆子痫、妊娠糖尿病等。2022年5月17日，Mirvie宣布完成6000万美元的B轮融资。本轮融资由Decheng Capital领投，BlackRock, Foresite Capital, General Catalyst, GV, Khosla Ventures,与Mayfield 跟投。截至目前，Mirvie共计完成9000万美元的融资，本次融资致使该公司估值达到1.55亿美元。在本月初，Mirvie的先兆子痫测试技术获得了FDA突破性设备指定。本轮融资筹集的资金将用于资助该项技术的10000人临床试验，为Mirvie的检测技术走向商业化提供重要支持。女儿的早产让生物工程师父亲开始技术研究在美国，每年有一千五百万婴儿早产(MIT Technology Review. 02.27.2019)，美国科学家，加州理工学院的生物工程师Stephen Quake的女儿Zoe就是其中之一。提前一个月来到世界的她，第一晚只能在保温箱度过。Quake看着保温箱里的女儿，和刚结束紧急破腹产手术的妻子，开始思考为何生产不能被更加准确的预测。在Zoe高中三年级的时候，Quake宣布自己开发出了一种母亲的RNA血液测试。通过对母亲血液中自由漂浮的RNA进行测序，Quake识别出七个与早产相关基因的表达变化，找到可能过早分娩的女性，给医生和新生儿家庭争取更多的准备时间。这样的液体活检技术在肿瘤早筛领域发展多年。在斯坦福大学学习应用物理和基因组技术的Maneesh Jain博士花了二十年的时间将液体活检技术商业化，期间担任一家肿瘤早筛液体活检公司的CEO。2018年，二位看到了该技术在这癌症与妊娠两个领域中“技术应用”和“资源分配”的差异，决定创立一个通过液体活检为女性提供怀孕健康支持的平台——Mirvie，Stephen Quake担任科学顾问委员会主席，Maneesh Jain担任首席执行官。宾夕法尼亚大学佩雷尔曼医学院的孕产妇胎儿医学医生Michal Elovitz在十多年前研究出预测孕妇早产风险的母体血液蛋白质，但检测单个蛋白的方法比较局限，不易于推广，而Quake和Jain的RNA检测技术引起了Elovitz的兴趣。加上多年的临床经验，Elovitz也看到了医生在妊娠并发症，如先兆子痫、妊娠糖尿病等方面的不准确干预，Elovitz加入Mirvie希望找到妊娠并发症的真正病因所在。Michal Elovitz医生如今担任Mirvie的首席医学顾问。Mirvie联合创始人兼首席执行官Maneesh Jain，首席医学顾问Michal Elovitz，联合创始人兼科学顾问委员会主席 Stephen Quake cfRNA预测胎龄成本更低，提前2个月识别自发性早产几千年来，了解怀孕的时间和进程一直是人们感兴趣的话题。古希腊人对胎儿发育的不同阶段就已经有了详细的描述，现在的生物学家虽然也拥有胎儿和胎盘发育的详细细胞与分子图谱，但目前并没有一种可靠预测胎龄的分子测试。人绒毛膜促性腺激素(HCG)和α胎蛋白的血液水平分别用于检测受孕情况和胎儿并发症，然而这两种分子检测都不能用于确定胎龄。根据孕妇最后一次月经期估算胎龄极不准确，超声成像目前是提供胎儿发育和胎龄信息的金标准，但在资源缺乏的地区并不总是负担得起，且不能预测自发性早产。不准确的胎龄测定可能会导致不必要的引产和剖腹产，进而延长产后护理且增加医疗费用。目前估计分娩日期的方法通常默认胎儿正常发育出生，并没有考虑会出现自发性早产的情况。实际上，H. Blencowe等人调差发现，早产每年影响全球约1500万新生儿。据美国医学研究所统计，早产是美国新生儿死亡和万年并发症的主要原因，其中2/3的早产是自发性早产。通过家族史或危险因素可以推测孕妇是否存在早产风险，但准确性有限；临床上有：超生测量宫颈长度(CL)或检测宫颈的胎儿纤维连接蛋白(fFN)的方法，但阳性预测值较低，且存在特异性。Stephen Quake博士带领的团队在一项针对31名健康孕妇的试点研究中发现，与胎盘基因相对应的无细胞RNA (cfRNA)可能在整个怀孕期间提供胎儿发育和胎龄的精准估计。通过测量母体血液中的cfRNA转录物，Quake团队确定了9种用于预测胎龄的cfRNA：CGA、CAPN6、CGB、ALPP、CSHL1、PLAC4、PSG7、PAPPA、LGLS14。此方法对胎龄估测的准确度与超声检测相当，但成本更低。cfRNA测量在预测胎龄中的应用第一阶段的实验完成了对足月生产的分娩时间预测，为了发现能够预测自发性早产的cfRNA转录物，Quake团队又对另外38名已知存在早产风险的孕妇(出现早期宫缩或有既往史)展开研究。参与其中的所有孕妇都完成了自然分娩(25例足月分娩，13例早产)，Quake团队将这些女性血浆中的cfRNA进行测序(RNA-seq)，最终发现7个cfRNA能够用来识别有早产风险的女性：CLCN3、DAPP1、PPBP、MAP3K7CL、MOB1B、RAB27B、RGS18，这些cfRNA能够在分娩前2个月准确识别出有自发性早产风险的孕妇。cfRNA测量在预测自发性早产风险中的应用Quake团队的研究实现了无创血液检测在预测胎龄与识别早产风险方面的作用。与现有方法相比，基于cfRNA的测试适用性更广，成本更低。 cfRNA揭示先兆子痫患病风险，获FDA突破性设备认证先兆子痫是妊娠期特有的一种多系统进展性疾病。其特点是妊娠20周后出现新发高血压和蛋白尿，或出现新发高血压和终末器官功能障碍伴或不伴蛋白尿。病情可呈持续性发展，严重影响母婴健康。孕产妇发病率和死亡率持续上升，先兆子痫是这一现状的主要驱动因素。然而，目前难以在临床表现之前通过病理生理学方法识别有风险的妊娠，医生通常采用询问风险因素来评估，先兆子痫既往病史作为头号危险因素却对初产妇起不到任何评估作用。Michal Elovitz医生带领团队对1840个不同人种的孕妇、2539个血浆样本展开研究。通过RT-qPCR检测，Elovitz团队证明了：偏离标准模型的cfRNA转录物可以在出现病变之前作为关键指标对先兆子痫进行预测。值得注意的是，cfRNA谱仅通过先兆子痫常见的分子机制来识别风险，并不包括种族、体重指数BMI、产科病史等临床变量。Elovitz团队鉴定出7个能够预测先兆子痫的cfRNA：CLDN7，PAPPA2，SNORD14A，PLEKHH1，MAGEA10，TLE6、FABP1。这7个cfRNA对先兆子痫的灵敏度为75%，阳性预测值为32.3%(s.d., 3%)，优于目前最先进的先兆子痫预测方法。这项技术目前已获得FDA突破性设备认证，Mirvie接下来将展开10000人的临床试验，提高检测效率，也期待获得新的突破。cfRNA预测先兆子痫的特征和模型性能比尔盖茨选择的“十大突破性技术”之一Mirvie将生物工程学、液体活检与临床妇产科结合，用专有的cfRNA检测技术为孕妇检测胎龄、评估早产风险、预测先兆子痫。Quake团队的血液测试技术被比尔盖茨评选为2019年人类10项突破性技术之一，单次测试的花费却不超过10美元。Mirvie实现了为女性提供怀孕健康的新机会，CEO Jain先生也表示公司下一步将会在妊娠糖尿病、胎盘植入等可能造成大出血的妊娠问题做出技术突破。Mirvie RNA平台根据每个妊娠情况的基本生物学原理，提前数月预测病发病“这个领域的许多科研成果并不像我们在癌症等领域所看到的那样发达，那些领域一直在获得大量的投资，”GV(Google Ventures)的普通合伙人Krishna Yeshwant说：“这意味着人们可以将这些不同领域的知识带入女性健康。”有创性产前诊断方法，如绒毛取材术、羊膜腔穿刺术和经皮脐血管穿刺等，在临床上暴露出孕妇伤害大、流产风险高、检测孕周偏晚等痛点；先兆子痫也只是通过临床表现进行诊断或患病史进行筛查，这一切被国内越来越多的医护人员和科研学者看到。POCT临床诊断设备研发商赛雷纳实现对母体外周血中游离胎儿细胞/DNA的准确鉴别，通过无创产检基因检测(NIPT)分析评估胎儿是否存在染色体或基因异常。奥丞生物自主研发的胎盘生长因子检测试剂盒(PLGF)获得NMPA批准，让国内先兆子痫的产前筛查有了突破性成果。由国家卫健委制定、国务院成立健康中国行动推进委员会统筹推出的《健康中国行动(2019-2030年)》明确指出：2022年、2030年我国孕产妇死亡率要求分别下降到18/10万及以下和12/10万及以下；产前筛查率分别达到70%及以上和80%及以上。再转向液体活检在中国的潜在市场空间，灼识咨询预计到2030年在癌症伴随诊断、微小残留病监测和癌症早筛早检等三个领域的潜在市场规模分别为45、150、 290亿美元，总体市场空间达约485亿美元，约合人民币近3400亿。癌症液体活检技术在国内日益成熟的临床应用和持续扩张的市场份额为填补产妇液体活检技术缺口带来一定希望，但目前最重要的还是要取得“孕妇血液中游离DNA和RNA识别与检测”的技术突破，孕产妇健康需要获得更多“目光”。*参考文献：Ngo, et al. Noninvasive blood tests for fetal development predict gestational age and preterm delivery. SCIENCE. 2018. SourceRasmussen, et al. RNA profiles reveal signatures of future health and disease in pregnancy. Nature. 2022. Source想要联系动脉网报道的企业，请点击文末左下方“阅读原文”填写表单，我们的工作人员将尽快为您服务。左右滑动查看更多近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

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