Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2024-10-03 DOI:10.1002/cti2.70011

Kathrin Kläsener, Nadja Herrmann, Liliana Håversen, Timothy Sundell, Martina Sundqvist, Christina Lundqvist, Paul T Manna, Charlotte A Jonsson, Marcella Visentini, Diana Ljung Sass, Sarah McGrath, Kristoffer Grimstad, Alaitz Aranburu, Karin Mellgren, Linda Fogelstrand, Huamei Forsman, Olov Ekwall, Jan Borén, Inger Gjertsson, Michael Reth, Inga-Lill Mårtensson, Alessandro Camponeschi

{"title":"Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells","authors":"Kathrin Kläsener, Nadja Herrmann, Liliana Håversen, Timothy Sundell, Martina Sundqvist, Christina Lundqvist, Paul T Manna, Charlotte A Jonsson, Marcella Visentini, Diana Ljung Sass, Sarah McGrath, Kristoffer Grimstad, Alaitz Aranburu, Karin Mellgren, Linda Fogelstrand, Huamei Forsman, Olov Ekwall, Jan Borén, Inger Gjertsson, Michael Reth, Inga-Lill Mårtensson, Alessandro Camponeschi","doi":"10.1002/cti2.70011","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p><i>In silico</i> analyses of patient samples, combined with <i>in vitro</i> experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447455/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Translational Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cti2.70011","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells.

Methods

In silico analyses of patient samples, combined with in vitro experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway.

Results

Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes.

Conclusion

The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

查看原文本刊更多论文

用单克隆抗体靶向 CD38 可破坏小儿伯基特淋巴瘤恶性 B 细胞的关键生存途径。

目的：小儿伯基特淋巴瘤（pBL）是最常见的儿童非霍奇金B细胞淋巴瘤。尽管大多数患儿的存活率令人鼓舞，但治疗复发/对现有疗法耐药的病例仍具有挑战性。CD38 是一种在 pBL 中高度表达的跨膜蛋白。本研究调查了CD38靶向单克隆抗体（mAbs）达拉土单抗和伊沙妥昔单抗在损害pBL恶性细胞的关键细胞过程和生存途径方面的有效性：方法：对患者样本进行硅学分析，结合使用拉莫斯细胞系进行的体外实验，评估达拉单抗和伊沙妥昔单抗对细胞增殖、凋亡和磷酸肌酸3-激酶（PI3K）通路的影响：结果：在破坏B细胞受体信号、减少细胞增殖和诱导细胞凋亡方面，伊沙妥昔单抗比达拉atumumab更有效。此外，伊沙妥昔单抗还能显著削弱 PI3K 通路，并诱导 pBL 细胞的代谢重编程。研究还发现，在pBL患者样本中，CD38和MYC的表达水平存在相关性，这表明CD38参与了关键的致癌过程：结论：该研究强调了 CD38 靶向 mAbs（尤其是伊沙妥昔单抗）在 pBL 中的治疗潜力。

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分钟内获得全文求助全文

来源期刊

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.