دورية أكاديمية

Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma

التفاصيل البيبلوغرافية
العنوان: Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma
المؤلفون: Margaux Lejeune, Murat Cem Köse, Mégane Jassin, Marie-Jia Gou, Amaury Herbet, Elodie Duray, Gaël Cobraiville, Jacques Foguenne, Didier Boquet, André Gothot, Yves Beguin, Marianne Fillet, Jo Caers
المصدر: HemaSphere, Vol 7, Iss 7, p e901 (2023)
بيانات النشر: Wiley, 2023.
سنة النشر: 2023
المجموعة: LCC:Diseases of the blood and blood-forming organs
مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5
الوصف: Despite the recent introduction of next-generation immunotherapeutic agents, multiple myeloma (MM) remains incurable. New strategies targeting MM-specific antigens may result in a more effective therapy by preventing antigen escape, clonal evolution, and tumor resistance. In this work, we adapted an algorithm that integrates proteomic and transcriptomic results of myeloma cells to identify new antigens and possible antigen combinations. We performed cell surface proteomics on 6 myeloma cell lines based and combined these results with gene expression studies. Our algorithm identified 209 overexpressed surface proteins from which 23 proteins could be selected for combinatorial pairing. Flow cytometry analysis of 20 primary samples confirmed the expression of FCRL5, BCMA, and ICAM2 in all samples and IL6R, endothelin receptor B (ETB), and SLCO5A1 in >60% of myeloma cases. Analyzing possible combinations, we found 6 combinatorial pairs that can target myeloma cells and avoid toxicity on other organs. In addition, our studies identified ETB as a tumor-associated antigen that is overexpressed on myeloma cells. This antigen can be targeted with a new monoclonal antibody RB49 that recognizes an epitope located in a region that becomes highly accessible after activation of ETB by its ligand. In conclusion, our algorithm identified several candidate antigens that can be used for either single-antigen targeting approaches or for combinatorial targeting in new immunotherapeutic approaches in MM.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2572-9241
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العلاقة: http://journals.lww.com/10.1097/HS9.0000000000000901Test; https://doaj.org/toc/2572-9241Test
DOI: 10.1097/HS9.0000000000000901
الوصول الحر: https://doaj.org/article/941162fc8eb943a5ac5f70af1a269293Test
رقم الانضمام: edsdoj.941162fc8eb943a5ac5f70af1a269293
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:25729241
00000000
DOI:10.1097/HS9.0000000000000901