Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-08 DOI:10.1080/17576180.2024.2407228

Fengying Zhu, Ya-Ping Tu, Callum Sloss, Yuemei Wang

{"title":"Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer.","authors":"Fengying Zhu, Ya-Ping Tu, Callum Sloss, Yuemei Wang","doi":"10.1080/17576180.2024.2407228","DOIUrl":null,"url":null,"abstract":"Aim: The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies.Materials & methods: An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients.Results: Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy.Conclusion: Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17576180.2024.2407228","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Aim: The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies.Materials & methods: An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients.Results: Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy.Conclusion: Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

评估叶酸受体α阳性卵巢癌患者的米尔韦妥昔单抗索拉坦辛免疫原性。

目的：本研究旨在评估四项临床研究中叶酸受体α阳性卵巢癌患者对抗体药物共轭物米尔韦妥昔单抗（MIRV）的免疫原性：开发并验证了一种检测 MIRV 抗药抗体 (ADAs) 的方法。还开发并验证了一种基于细胞的方法，用于检测中和抗 MIRV 抗体 (NAbs)。四项临床研究对 734 名患者进行了 ADAs 和 NAbs 评估：结果：在所有研究中，MIRV 的免疫原性都很低，7.8% 的患者有治疗引起的 ADA，7.2% 的患者有治疗未影响的 ADA，0.5% 的患者有治疗增强的 ADA。ADA 阴性和 ADA 阳性患者的 MIRV 谷浓度相当。有限的数据表明，MIRV ADA 可能与疗效下降有关。由于 NAb 阳性个体的数量非常有限，因此无法就 NAb 对疗效的影响得出结论：验证试验和来自 MIRV 临床研究的数据都表明，这些检测方法适用于 MIRV ADAs 和 NAb 的检测，且结果可靠。在未来的临床试验中，这些经过验证的检测方法将继续用于监测 MIRV 的免疫原性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.

期刊最新文献

Management of Cholesteatoma: Hearing Rehabilitation. Congenital Cholesteatoma. Evaluation of Cholesteatoma. Management of Cholesteatoma: Extension Beyond Middle Ear/Mastoid. Recidivism and Recurrence.